Current insights into insect immune memory

Virtually all living organisms possess some form of immune system, which ensures the recognition of self from non-self and protects the integrity of the organism and its genetic information. Individual immune mechanisms have evolved over millions of years of coevolution between the host’s immune system and the pathogens attempting to evade it (Müller et al., 2018). Acquisition of experience from the initial contact with the pathogen, therefore, represents the crucial advantage for hosts that can gain resistance to reinfections (Palmieri et al., 2021).

In nature, we can observe various sophisticated strategies that allow organisms to gain a certain degree of immune experience at both the systemic and cell-autonomous levels (Divangahi et al., 2021). While the term ‘acquired immunity’ was previously used almost exclusively to refer to adaptive immunity in jawed vertebrates, it is now applied more broadly to encompass various forms of acquired immune experience (Little et al., 2005; Rimer et al., 2014; Cooper and Eleftherianos, 2017). Currently, three basic categories of acquired immune responses (immune priming, immune training, and immune memory; Box 1) are distinguished according to the character and specificity of the initial immune response (Tang et al., 2023; Vuscan et al., 2024; Netea et al., 2019; Figure 1). The original anthropocentric belief that only vertebrates with adaptive immune systems can form specific and long-lasting immune memory is incorrect. Advances over the last two decades in comparative and evolutionary immunology have revealed complex mechanisms underlying the adaptability of immune response in prokaryotic bacteria and archaea, and various degrees of acquired immunity can be observed in almost all eukaryotes (Newsom et al., 2020; Bagasra and Prilliman, 2004; Gomes et al., 2022).

Figure 1

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Whole-genome sequencing and comparative analysis of hundreds of prokaryotic organisms have led to the discovery of genomic islands that accumulate immune-related genes, enabling the identification of more than 150 distinct prokaryotic immune mechanisms (Bernheim et al., 2024). Notably, many of these mechanisms are also present to some extent in eukaryotes, indicating that particularly cell-autonomous immune mechanisms are remarkably conserved across the tree of life (Mayo-Muñoz et al., 2023). The prevailing hypothesis for this phenomenon is that immune mechanisms that evolved during the rapid evolution of prokaryotes, as protection against mobile genetic elements and other pathogens, were later adopted and repurposed by eukaryotic immune systems. The acquisition of these immune traits likely occurred through horizontal gene transfer mediated by retrotransposons, highlighting the central role of domesticated mobile genetic elements in the evolution of the eukaryotic immune system (Wein and Sorek, 2022).

A particularly interesting example of an adaptive immune mechanism in prokaryotes is the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system. This system is widely present in most archaea and many bacteria, where it serves as a defense mechanism against bacteriophages (Rath et al., 2015). When a bacterium or archaeon is infected by a bacteriophage, it can recognize the foreign nucleic acids, cleave them into smaller fragments, and integrate these fragments into its own genome. Viral DNA fragments are inserted into a specific region of the host genome known as CRISPR, which acts as a repository of previous viral encounters (Wang et al., 2022).

Upon subsequent viral infection, the CRISPR locus is transcribed, producing CRISPR-pre-mRNA, which is then cleaved into individual CRISPR RNAs. These short RNA fragments guide Cas nucleases to perform sequence-specific cleavage of viral genetic material (Hille et al., 2018). This sophisticated mechanism is widely regarded as a clear example of adaptive immunity since the integration of viral sequences into the host genome serves as a form of immune memory, while sequence-specific cleavage ensures the specificity of the immune response (Jiang and Doudna, 2017). Interestingly, key enzymes that protect prokaryotes from mobile genetic elements are co-opted transposases derived from retrotransposons (Koonin and Krupovic, 2015).

A similar phenomenon is observed in the adaptive immune system of jawed vertebrates, where the enzymes responsible for somatic recombination (Rag1 and Rag2) in T and B lymphocytes are derived from the Transib family of retrotransposons (Huang et al., 2016). Another example, which will be discussed in detail later in this review, is the adaptive antiviral immunity in insects. In this system, endogenous transposons Ty1 and Ty3 play a central role in acquiring copies of viral nucleic acids and integrating them into the genome, thus creating a long-lasting and heritable immune memory (Saleh et al., 2009; Tassetto et al., 2017). These examples reveal intriguing parallels in the convergent evolution of mechanisms of acquired immunity (Eaglesham and Kranzusch, 2024), all of which exploit the enzymatic activities of genes acquired from domesticated retrotransposons to establish immune memory by modifying host genomic information. Comparative and evolutionary immunology may offer valuable insights into the discovery of as-yet-unidentified mechanisms of immune memory.

Insect immune system

Insects are the most abundant group of animals on Earth (Stork, 2018), and like other animals, they are exposed to a wide range of pathogens throughout their lifetimes, including viruses, bacteria, fungi, protozoa, nematodes, and parasitoids (Federici, 2009). While certain pathogens can cause significant declines in entire insect populations, others are tolerated to varying degrees. In such cases, insects can act as reservoirs for these pathogens, serving as vectors that facilitate their amplification and transmission, including to humans (St Leger, 2021).

In insects, the primary immune defense is provided by the cuticle, which acts as a physical barrier, offering strong protection against most pathogens in the environment. Consequently, the most common routes of infection are through wounds, the digestive system, or the tracheal system. Once the cuticle is breached, immune cells are activated, triggering both cellular and humoral immune responses (Buchon et al., 2014; Figure 2).

Figure 2

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The insect innate immune system is largely based on evolutionarily conserved pathways, which are also found, to some extent, in mammals. The cellular branch includes various effector immune cells, known as hemocytes, which perform distinct functions during the immune response, such as phagocytosis (plasmatocytes), encapsulation (lamellocytes), activation of phenoloxidases (crystal cells), degranulation (granulocytes), or the release of extracellular traps (Mahanta et al., 2023). In addition, some insect species possess specialized immune cell types, such as spherulocytes, oenocytoids, coagulocytes, adipohemocytes, and thrombocytoids, which further contribute to pathogen elimination, wound healing, metabolic homeostasis, as well as nutrient transport (Eleftherianos et al., 2021). Though not present in all insect species, an alternate approach to pathogen neutralization is the formation of extracellular traps. These extracellular web-like structures, composed of double-stranded DNA, histones, elastase, and myeloperoxidase, serve to trap, immobilize, and kill pathogens (Nascimento et al., 2018). Although insect immune cell types and their functions are less diverse than those in vertebrates, the key signaling pathways and transcription factors involved in phagocytosis (Melcarne et al., 2019), hematopoiesis (Banerjee et al., 2019), cell proliferation, and differentiation (Evans et al., 2003) have remained conserved for over 550 million years of evolution.

Pathogens are detected by pathogen recognition receptors that can be classified into several groups, such as NOD-like receptors, C-type lectins, thioester-containing proteins, scavenger receptors, peptidoglycan recognition proteins, Toll-like receptors, or Gram-negative-binding proteins. These receptors activate general immune-related signaling pathways, such as Toll, IMD, Janus kinase/signal transducers and activators of transcription (JAK-STAT), or Jun N-terminal kinase (JNK). While Gram-positive bacteria and fungi predominately activate the Toll pathway, Gram-negative bacteria induce the IMD signaling pathway (Browne et al., 2013). Activation of cellular immunity is often associated with increased proliferation of immune cell precursors and their differentiation. These processes are coordinated by specific transcription factors and signaling pathways, including erythroid transcription factors, vascular endothelial growth factor, JAK-STAT, and JNK (Banerjee et al., 2019; Evans et al., 2003).

When encountering foreign objects too large for phagocytosis, such as parasitoid eggs or nematodes, insects utilize encapsulation and melanization (Bilandžija et al., 2017). The surface antigens of the parasitoid are recognized by macrophage-like plasmatocytes, which release signaling factors that trigger the extensive differentiation of progenitor prohemocytes and plasmatocytes into lamellocytes (Nakhleh et al., 2017). These large, sheet-like cells completely encase the foreign object in successive layers and secrete prophenoloxidases within the capsule. These enzymes catalyze the conversion of the amino acids phenylalanine and tyrosine into melanin, producing toxic free radical by-products that help eliminate the pathogen (Tang, 2009).

Insects constantly face an incredibly wide range of DNA and RNA viruses, and, therefore, it is not surprising that the antiviral response of insects is both complex and highly developed. The conserved intracellular immune response based on RNA interference (RNAi) remains the most thoroughly studied antiviral mechanism in insects (Gammon and Mello, 2015). In this pathway, viral double-stranded RNA is cleaved by the endoribonuclease Dicer into short small interfering RNA (siRNA) fragments. Dicer, together with the RNA-dependent nuclease Argonaut, forms the RNA-induced silencing complex (RISC), which facilitates the sequence-specific recognition and cleavage of viral nucleic acids (Leggewie and Schnettler, 2018).

Many immune and repair signaling pathways, such as Toll, IMD, and JAK-STAT, have also been implicated in antiviral defense. Activation of these pathways triggers a systemic antiviral response, which includes increased production of antimicrobial peptides, reactive oxygen species (ROS) and reactive nitric species, as well as the elimination of virus-infected cells through autophagy and efferocytosis by macrophage-like plasmatocytes (Kingsolver et al., 2013). While the interferon response characteristic of mammalian species has not been identified in insects, recent findings suggest that the cGAS-like receptor STING-Relish pathway plays a central role in general antiviral defense in Drosophila. In mammals, the cGAS-STING is a major component of the antiviral response to DNA viruses, leading to the activation of an interferon-based response. Similarly, in insects, it has been documented that STING signaling activates the IMD pathway transcription factor Relish to regulate the expression of genes potentially involved in antiviral defense (Goto et al., 2018; Decout et al., 2021).

The insect immune response is not solely dependent on the activity of the immune system itself, but requires coordinated adjustments across virtually all organs and tissues. Cytokines and metabokines produced by activated immune cells during an immune threat play a central role in orchestrating this coordination (Bajgar et al., 2021). Similar to mammalian macrophages, insect plasmatocytes undergo a fundamental metabolic rewiring in response to acute bacterial infection, shifting their predominant ATP metabolic pathway from oxidative phosphorylation to aerobic glycolysis (Krejčová et al., 2019). This metabolic adaptation provides sufficient energy and precursors for the production of ROS and other bactericidal effectors, though it also makes plasmatocytes highly dependent on external nutrient resources. To secure these resources, plasmatocytes secrete various factors, such as Imaginal morphogenesis protein late 2, to induce nutrient mobilization from the central metabolic organ while limiting their consumption by peripheral nonimmune tissues. Interestingly, this metabolic adaptation appears to involve the suppression of insulin signaling (Krejčová et al., 2023).

When introducing the insect immune system, the humoral branch cannot be omitted. It is responsible for producing a wide range of bactericidal substances, such as antimicrobial peptides, clotting factors, and signaling molecules. During systemic infection, antimicrobial peptides are rapidly expressed by immune cells and the fat body (Zhang et al., 2021). Due to their positive charge, these peptides act as opsonizing factors, embedding themselves in the hydrophobic portion of bacterial or fungal membrane. This facilitates recognition by immune cells, destabilizes the pathogen’s membrane, and ultimately leads to cell death (Dho et al., 2023).

Another common antimicrobial strategy in insects involves the coagulation of hemolymph, commonly referred to as clotting. Initially, the wound is covered by clotting proteins that are abundant in the hemolymph, such as thioester-containing proteins, integrins, lectins, lipoproteins, and storage peptides. These molecules are cross-linked by transglutaminase, which is homologous to factor XIIIa, a key component of the vertebrate coagulation cascade. As the process continues, the soft clot hardens through phenoloxidase-dependent cross-linking, resulting in hemolymph coagulation that restricts bacterial motility and division (Aprelev et al., 2019).

In addition to these intricate innate immune mechanisms, a growing body of evidence supports the existence of acquired immune mechanisms in insects. Although immune ‘adaptability’ in insects was not previously considered, presumably due to their shorter lifespan and thus the belief that they do not require immune memory, numerous documented cases of acquired immunity in insects now exist. While several insightful reviews have explored this topic in recent years (Cooper and Eleftherianos, 2017; Prakash and Khan, 2022), here we provide a systematic review of well-documented experimental evidence of acquired immunity in insects, with an emphasis on immune memory. Furthermore, we delve into the potential underlying mechanisms of antiviral and antibacterial immune memory and highlight unresolved questions that should be addressed in future research, possibly through the use of Drosophila melanogaster, which is exceptionally suited for genetic dissection of immune pathways. Finally, we discuss future directions for the field and explore how knowledge on innate immune memory mechanisms could inform the potential for insect vaccination.

The ability of the insect immune system to develop some form of acquired immunity has been documented in a wide range of species (Cooper and Eleftherianos, 2017; Kurtz and Franz, 2003; Trauer-Kizilelma and Hilker, 2015; Freitak et al., 2009; Figure 3). However, the experimental designs used in these studies differ significantly in several key aspects. These include the identity of the pathogen (bacteria, viruses, parasites, fungi), the pathogen dose, the use of homologous (the identical pathogen used twice) versus heterologous (a different pathogen used for the first and second exposure) challenges, the developmental stage of the host, and the interval between the first and second pathogen encounters. In the following paragraphs, we aim to focus mainly on documented cases of immune memory in insects. However, the design of some studies does not allow us to clearly distinguish between different types of acquired immunity.

Figure 3

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To assess the ability to develop specific immune memory and distinguish it from other types of acquired immunity, we suggest following several key principles when designing an infection assay. First, the pathogen used in both the first and second challenges must be identical (homologous infection). To distinguish immune memory from immune training, a different pathogen should also be used for the second challenge. If the second challenge results in improved resistance to this different pathogen, it suggests immune training rather than memory. The nature of the pathogen itself should also be considered as Gram-positive and Gram-negative bacteria, fungi, and viruses activate different immune pathways (Wang et al., 2010; Cheng et al., 2016). Additionally, the infection dose and route should be carefully chosen as they can influence the activation of downstream signaling pathways and determine which components of the immune system are engaged (Pereira et al., 2024). It is also important to consider whether the pathogen is naturally associated with the insect species in question as some species may exhibit high tolerance to certain pathogens. Tolerance refers to the ability of an organism to limit the negative fitness consequences of infection without necessarily reducing the pathogen load (Schneider, 2021). Even the genetic identity of the pathogen can be critical as different strains may vary in antigenicity or induce cross-reactive immunity (Johnson et al., 2012; Roth et al., 2009). Crucially, the interval between the first and second doses must be long enough to allow for the complete clearance of the pathogen from the organism and to give the immune system time to develop immune memory. If the pathogen persists, the immune system may remain in an activated state, making it difficult to determine whether a true memory response or simple immune priming is occurring. Therefore, immune activation readouts should return to baseline levels before administering the second dose as immune memory functions on biphasic principles.

In the following paragraphs, we focus on documented cases of acquired immunity with emphasis on immune memory, followed by documented cases of acquired immunity across life stages and across generations. We begin with D. melanogaster, the most tractable insect model organism (Arch et al., 2022).

The first study to document the existence of some form of immune adaptivity in D. melanogaster was published in 2005. In this study, the authors demonstrated that flies that were first inoculated with an avirulent strain of Pseudomonas aeruginosa mount an increased resistance to a highly virulent strain. However, the second bacterial dose was administered no later than 24 hours after the initial exposure (Apidianakis et al., 2005). While there is no doubt that survival rates improved, this may be attributed to immune priming rather than immune memory, given the extremely short time window between exposure to the low-virulence and virulent strains. This suggests that immune activation did not have sufficient time to return to baseline. In a follow-up study, the time interval between doses was extended to 11 days; however, by day 10, the bacteria were still present in the system, which again suggests priming rather than immune memory. Similar priming effects have also been observed in numerous other studies, achieved through both systemic and oral administration (Christofi and Apidianakis, 2013; Cabrera et al., 2023).

The study by Pham and colleagues may have more testimonial value regarding immune memory in D. melanogaster. Flies primed with either a sublethal dose or heat-killed Streptococcus pneumoniae were protected against a lethal challenge of the same bacterium administered 7 days later, allowing sufficient time for pathogen clearance. Since this protection was not observed against other selected pathogens, it suggests a highly specific immune response rather than a general activation of antibacterial immunity. A similar effect was achieved by administering a sublethal dose of the natural fungal pathogen Beauveria bassiana, which provided protection against a subsequent lethal dose of the same fungus. However, the ability to develop protection against future pathogen encounters may not be universal for all pathogens as administration of heat-killed Salmonella typhimurium, Listeria monocytogenes, and Mycobacterium marinum did not confer protection against subsequent lethal challenges with these respective bacteria (Pham et al., 2007).

Many studies on insect immune memory have also been conducted using models other than D. melanogaster (Freitak et al., 2009; Wang et al., 2010; Cheng et al., 2016; Pereira et al., 2024). A remarkably high degree of specificity of immune memory has been documented in Tribolium castaneum, whose immune system can discriminate between closely related bacterial strains of Bacillus thuringiensis (Roth et al., 2009; Futo et al., 2017). Narrow specificity and increased protection have also been observed in the bumblebee, Bombus terrestris, where the immune memory lasts for several weeks after clearance of bacteria from the first exposure (Sadd and Schmid-Hempel, 2006).

Interestingly, immune memory in insects may potentially persist across different life stages. Mondotte and colleagues conducted trans-stadial assays, revealing that adult flies orally infected with Drosophila C virus during the larval stage exhibited increased tolerance to subsequent reinfections with the same virus. Furthermore, when adult flies derived from larvae infected with Drosophila C virus were reinfected with different viruses, their survival rates were comparable to those of the control group. This indicates that the acquired protection is both virus-specific and sequence-specific (Mondotte et al., 2018). Trans-stadial acquired immunity has also been documented in Aedes aegypti, where infection of larvae with inactive dengue virus has been shown to protect against subsequent infection in adult mosquitoes (Vargas et al., 2020). Similar protective effects in adults have also been observed following exposure of A. aegypti larvae to Escherichia coli (Moreno-García et al., 2015). Trans-stadial protection has also been documented in another mosquito, Anopheles arabiensis. In this study, larval exposure to Streptococcus pyogenes or E. coli led to increased longevity of adult females challenged with the respective pathogen (Patel and Oliver, 2024). An intriguing model for investigating acquired trans-stadial immunity during host–parasite interaction is Tribolium confusum infected with the parasite Gregarina minuta because the gut parasites are naturally shed during metamorphosis along with the gut lining. Indeed, this model has shown that adult beetles infested with G. minuta display enhanced survival resistance when infected as larvae, highlighting the persistence of immune protection across life stages (Thomas and Rudolf, 2010).

Intriguingly, several studies have documented the ability of insects to pass immune experiences acquired during pathogen exposure to their offspring, a phenomenon known as transgenerational immune priming (TgIP). Since mounting an immune response is connected with significant energy costs, TgIP is likely to evolve in environments where offspring have a high probability of encountering the same pathogen as their parents (Thomas and Rudolf, 2010). This is especially plausible in social insects, where worker offspring remain in the natal nest. In 2014, a study was published in which researchers challenged honeybee queens by injecting a vegetative form of heat-killed Paenibacillus larvae, the causative agent of American foulbrood (Genersch, 2010). Although adult honeybees are resistant to P. larvae infection, they act as vectors, transmitting the disease to the brood (Fries et al., 2006). The larvae of immunized queens were subsequently fed a diet containing P. larvae spores, that is, the infectious stage. It has been shown that these individuals display improved survival compared to larval progeny of nonimmunized queens. This enhanced survival was presumably due to a threefold increase in the number of differential hemocytes (all hemocyte types except for prohemocytes) (Hernández López et al., 2014). TgIP has also been repeatedly documented in another hymenopteran species, the bumblebee (B. terrestris). When queens were challenged with heat-killed Arthrobacter globiformis, both their eggs and progeny workers exhibited significantly higher antibacterial activity when injected by lipopolysaccharides, compared to controls (Sadd and Schmid-Hempel, 2007). However, such TgIP has been connected with certain costs since these individuals were more susceptible to a pathogen distinct from maternal challenge, the trypanosome parasite Crithidia bombi (Sadd and Schmid-Hempel, 2007). The costs of TgIP have also been investigated in tobacco hornworm Manduca sexta, where female offspring of immunized parents laid fewer eggs than those derived from control parents (Trauer and Hilker, 2013).

Female TgIP is in agreement with parental investment theory, according to which females invest more into rearing their offspring than males. Nonetheless, as evidenced by research conducted on the red flour beetle T. castaneum, TgIP is not restricted to maternal effects. After parental exposure to heat-killed E. coli or B. thuringiensis, TgIP occurs through fathers as well as mothers (Roth et al., 2010). Similar results were obtained in another coleopteran species, the yellow mealworm beetle Tenebrio molitor, where adult males and females were immune-challenged with lipopolysaccharide (LPS), and their progeny showed improved response to LPS. However, the underlying mechanism of TgIP in mothers and fathers seems to be different as stimulation of different immune effectors in the offspring has been recorded, and the duration of the protection also differs according to the sex of the challenged parent. While the offspring of LPS-treated mothers displayed an increased number of hemocytes and unaffected phenoloxidase and antibacterial activity before and after immune stimulation, offspring males showed no alterations in the number of hemocytes or phenoloxidase and antibacterial activity, but they displayed the ability to develop a stronger immune response mediated by the prophenoloxidase. Nonetheless, these effects were observed only in offsprings laid within the first 4 days after paternal challenge (Zanchi et al., 2011). A study published by Patel and Oliver suggests that TgIP in An. arabiensis may be influenced by the insecticide-resistant phenotype as protection was observed in insecticide-susceptible An. arabiensis but not in their resistant counterparts (Patel and Oliver, 2024).

Evidence of TgIP has also been found against viral pathogens. Offspring of Indian meal moth (Plodia interpunctella) parents exposed to a low dose of their natural DNA virus during the larval stage were less susceptible to viral challenge (Tidbury et al., 2011). Further insights into TgIP were provided by a study published by Mondotte and colleagues, which clearly demonstrated that the acquired immune protection is both virus- and sequence-specific, persisting across generations. Using D. melanogaster and A. aegypti as models, the authors revealed that the offspring of immune-challenged parents inherit viral DNA and exhibit upregulation of genes related to chromatin and DNA binding (Mondotte et al., 2020). Similar results were obtained in a recent study by Rodriguez-Andres and colleagues, who documented that A. aegypti mosquitoes infected with arboviruses can transmit specific immunity to their offspring (Rodriguez-Andres et al., 2024). Additionally, alterations in the epigenetic landscape, specifically DNA methylation and histone acetylation, were detected in the F1 generation of parents fed non-pathogenic E. coli or the entomopathogen Serratia entomophila (Gegner et al., 2019). These findings highlight the role of epigenetic mechanisms in TgIP.

Insect’s adaptive antiviral immunity

Insects frequently face infections from various DNA and RNA viruses (Bruner-Montero et al., 2023). The life cycle of insect viruses does not differ significantly from that of viruses infecting other eukaryotes. Upon entry into a host cell, viruses hijack the host’s transcription and translation machinery with the goal of replicating their genetic material and synthesizing proteins for the capsid, facilitating further viral propagation (Wang et al., 2024). Once a cell is infected, it activates several cell-autonomous antiviral immune mechanisms, relying primarily on RNAi, stalled translation, nucleotide-based antiviral strategies, induction of autophagy, and ultimately, apoptosis (Tafesh-Edwards and Eleftherianos, 2020). Although these antiviral strategies significantly reduce virus replication in infected cells, they are not sufficient to make individuals fully resistant to viral infection.

Recent discoveries have shown that the systemic immune response is critical for host resistance to viral infections in Drosophila (Kingsolver et al., 2013). Virus-infected cells commonly activate the transcription factors Hop and Dome, leading to increased production of unpaired family cytokines (Upd1, Upd2, Upd3). Elevated levels of these cytokines in circulation activate macrophage-like plasmatocytes via the JAK-STAT signaling pathway, attracting them to virus-infected tissues (Sabin et al., 2010). The elimination of virus-infected apoptotic cells by activated plasmatocytes has been shown to be crucial for viral resistance in Drosophila (Saleh et al., 2009). However, plasmatocytes do not simply degrade all engulfed material; the presence of viral double-stranded RNA in the phagolysosome leads to permeabilization of its membrane and acquisition of viral genetic information (Tanaka et al., 2024). Plasmatocytes then use viral RNA as a template for reverse transcription, integrating fragments of complementary antisense viral DNA into their genomes (Tassetto et al., 2017). Since eukaryotic cells lack the enzymes necessary for these processes, they are facilitated by the activity of domesticated retrotransposons. The exact mechanism by which retrotransposons are engaged during infection has not yet been clarified. Nevertheless, retrotransposon activity increases more than 20-fold in plasmatocytes upon viral infection, and mere inhibition of retrotransposons completely abolishes the host’s resistance to infection. Sequencing of circular DNA from infected plasmatocytes reveals that virus-derived DNA is commonly flanked by sequences from Ty2 and Ty3 retrotransposons of the LTR family (Roy et al., 2020).

Viral RNA, integrated into specific regions of the host genome as endogenous viral element (EVE), serves as a template for producing secondary viral DNAs (svDNAs) (Tassetto et al., 2017). Expression of svDNAs subsequently provides cells with cell-autonomous resistance to viral infection as it primes the activation of Dicer and Argonaute proteins, which together form the RISC that governs sequence-specific elimination of viral RNA (van Rij et al., 2006). Additionally, plasmatocytes disseminate svDNA systemically, enclosed within extracellular vesicles or via tunneling nanotubes, along with activating cytokine signaling (Tassetto et al., 2017). Thus, plasmatocytes, even without being infected themselves, can amplify viral DNA and spread it as a form of prophylaxis to other cells, enabling them to acquire resistance against specific viruses (Mondotte et al., 2020; Figure 4).

Figure 4

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Similar to the CRISPR-Cas system, insect antiviral immune memory is based on the integration of viral sequences into the genome, which is later used for sequence-specific elimination of viral nucleic acids. Notably, the integration of viral DNA into the host genome also provides insects with transgenerational adaptive immunity (Mondotte et al., 2020; Rodriguez-Andres et al., 2024).

Despite certain variations in the molecular mechanisms, this general process appears to be widespread among insects. Comparisons of small RNAs produced from EVE regions in different insect species indicate that analogous mechanisms likely occur in ants (Hymenoptera), beetles (Coleoptera), aphids (Hemiptera), butterflies (Lepidoptera), mosquitoes and flies (Diptera), and even ticks (Ixodida, Arachnida, Chelicerata) (Gilbert and Belliardo, 2022). Recently, an analogous mechanism has also been identified in crustaceans, suggesting that the mechanism of antiviral immune memory may be common across most arthropods (Taengchaiyaphum et al., 2021).

In some of these species, EVE transcription gives rise not only to siRNA but also to longer transcripts known as Piwi-interacting RNAs (piRNAs). piRNAs bind to RISC complex proteins, Piwi (PIWI) and Aubergine (AUB), and enter the secondary piRNA biogenesis pathway in the cytosol, also known as the ‘ping-pong’ pathway (Tassetto et al., 2019). This allows the cell to amplify the signal and produce a much larger quantity of protective RNA fragments, which confer viral resistance and spread this resistance to other cells. This mechanism may provide mosquitoes with a heightened ability to resist viral infections without displaying any obvious pathological phenotypes. This aligns with the persistence of viral infections in these species, which is associated with their capacity to transmit a variety of viral diseases (Trammell and Goodman, 2021).

Evidence of sequence-based adaptive immune memory in insects raises the question of whether an analogous antiviral strategy may also occur also in mammals. Although experimental evidence for such a mechanism is currently lacking, there are indications that a similar mechanism might exist in mammals but is overshadowed by other dominant antiviral immune systems. Recent findings highlight the importance of cellular immunity, specifically the RNAi cascade, in antiviral defense mechanisms (Berkhout, 2018). Studies have documented that in mice viral infections are accompanied by the systemic spread of virus-derived small interfering RNAs via extracellular vesicles, which provide recipient cells with acquired resistance to subsequent viral infections (Zhang et al., 2022). However, contradictory findings in mammals suggest that Dicer exhibits negligible enzymatic activity in virus-infected cells, and its knockdown does not substantially affect viral load (Berkhout, 2018; Wang and Li, 2024). This phenomenon certainly warrants further investigation.

Insect’s adaptive antibacterial immunity

While the mechanism of antiviral immune memory formation is relatively well understood, the mechanisms underlying antibacterial immune memory remain more elusive. Nevertheless, we can assume that the formation of antibacterial immune memory would still involve phases of antigen acquisition, development of specificity, and memory maintenance.

Once bacteria breach primary immune barriers, they are recognized by professional phagocytes, which engulf and eliminate them in the phagolysosome. In contrast to mammals, where antigen acquisition from the phagolysosome of macrophages is well understood, this process remains largely unexplored in insects (Hultmark and Borge-Renberg, 2007). Although insects lack the major histocompatibility complex (MHC) and tapasin (Tap) genes, essential for canonical antigen presentation in mammals, certain evidence suggests that other components of the antigen processing machinery may be conserved. This is demonstrated by the fact that simply expressing these two genes heterogously in Drosophila S2 cells, derived from embryonic macrophages-like cells, enables them to present antigens on their surface (Ortmann et al., 1997). Therefore, we may assume that insect macrophage-like plasmatocytes process antigens similarly to their mammalian counterparts and present them to other immune cells in the body through a noncanonical pathway. Recent studies in mice have shown that mammalian macrophages disseminate antigens via extracellular vesicles, encapsulated within multilamellar bodies, or through a process known as eruptophagy, where the phagolysosome’s contents are released directly into the extracellular space (Smith et al., 2017; El Safadi et al., 2024; Lindenbergh and Stoorvogel, 2018). It is plausible that these primitive methods of antigen dissemination represent ancestral forms, with the addition of tapasin and MHC complexes evolving later alongside vertebrate adaptive immunity (Kaufman, 2018). This idea aligns with numerous observations in insects, where circulating bacterial antigens have been found in complexes with hemolymph proteins such as lipoproteins, vitellogenins, and several storage proteins (Salmela et al., 2015; Kato et al., 1994; Kanost and Zhao, 1996). However, further research on antigen processing and dissemination in insects is necessary.

A crucial step in forming immune memory is the recognition of pathogen surface antigens, similar to how multivariant immunoglobulin domains of antibodies function in vertebrates. Insects possess numerous genes containing immunoglobulin domains capable of binding bacterial antigens, among which the gene coding for Down syndrome cell adhesion molecule (Dscam) is particularly noteworthy (Watson et al., 2005). Dscam consists of extracellular, transmembrane, and cytosolic regions. The extracellular part of Dscam contains 10 immunoglobulin domains and 6 fibronectin type III repeats (Wang et al., 2012). Three of the immunoglobulin domains (2, 3, and 7) are encoded by multivariant exons (4, 6, and 9), which, in Drosophila, have 12, 48, and 33 alternative variants, respectively (Wojtowicz et al., 2007). While the general structure of Dscam is conserved across arthropods, the number of multivariant exons varies significantly among species (Ng and Kurtz, 2020). Individual DSCAM variants are produced through mutually exclusive alternative splicing, which ensures that only one variant from each multivariant exon is included in the final mRNA (Graveley, 2005). Consequently, Dscam can generate up to 19,008 (12 × 48 × 33) immunoglobulin domain variants, with additional variability arising from alternative splicing of exon 17, producing either membrane-bound or secreted forms (Celotto and Graveley, 2001; Figure 5).

Figure 5

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Drosophila Dscam is the gene with the highest number of alternative transcripts in animals, drawing significant scientific attention to the mechanisms regulating such a complex process. Inclusion of a single variant from a multivariant exon is achieved through the pairing of a ‘docking sequence’ at the end of the previous exon with a ‘selector sequence’ preceding each variant in the specific multivariable exon (Graveley, 2005). While the docking sequence interacts with a serine-arginine protein (SR-protein) to initiate the inclusion of the following exon, selector sequences are occupied by heterogeneous nuclear ribonucleoproteins (hnRNPs), which inhibit the inclusion of specifically occupied variants through steric hindrance (Olson et al., 2007). This process is further complicated by the influence of intronic RNA secondary structures called ‘inclusion RNA stem-loops’ (iStems) (Kreahling and Graveley, 2005). Moreover, it seems that each of the three multivariant exons shows specific characteristics in the alternative splicing mechanism (Ustaoglu et al., 2019; McManus and Graveley, 2011), which aligns with recent identification of more than twelve RNA-binding proteins involved in Dscam alternative splicing in S2 cells (Brooks et al., 2015).

In addition to the variability of Dscam in its immunoglobulin domains, there is also diversity in its cytosolic tail. It has been reported that alternative exon skipping and selection of alternative splicing sites for exons 18 and 23 generate eight different variants of Dscam cytosolic tail. This diversity may play an important role in intracellular Dscam signaling, a topic to be discussed later; however, no experimental data are currently available on this aspect (Sachse et al., 2019).

Dscam plays a dual role in insects; in addition to its function in immune response, it is essential for the development of the central nervous system (CNS) (Schmucker et al., 2000). The combination of several Dscam splicing variants provides each neuron in the Drosophila CNS with a unique recognition code (Hattori et al., 2007). Each DSCAM variant can form homodimeric bonds with another DSCAM molecule containing identical domains, allowing neurons to recognize their own cellular surfaces. This homodimeric interaction triggers intracellular signaling, leading to the remodeling of the actin cytoskeleton and repulsion of cellular extensions (Wojtowicz et al., 2004). This process prevents neurons from forming self-stimulating loops as they create complex structures in the developing CNS.

The role of Dscam in immune responses to bacterial pathogens is of particular interest. It has been shown that Dscam is highly expressed in Drosophila plasmatocytes during bacterial infection (Celotto and Graveley, 2001). Both circulating and membrane-bound forms of DSCAM are produced by plasmatocytes, facilitating the opsonization and phagocytosis of pathogens (Watson et al., 2005). It is believed that the binding of DSCAM to a pathogen alters its tertiary structure, allowing it to be recognized by membrane-bound DSCAM, which facilitates internalization through phagocytosis (Dong et al., 2006; Wan et al., 2023). It remains unclear whether each DSCAM variant has its own receptor and whether internalization requires homodimeric binding, or whether a general membrane-bound DSCAM can mediate internalization of any DSCAM variant. However, both circulating and membrane-bound forms of DSCAM are necessary for combating bacterial infections (Li, 2021; Li et al., 2019).

During immune responses, Dscam undergoes alternative splicing, enabling plasmatocytes to produce nearly the full spectrum of DSCAM variants. However, this alternative splicing is not a random process in plasmatocytes. Infection by a specific pathogen results in the selection of specific Dscam variants that exhibit particularly high affinity for the pathogen’s surface antigens (Meijers et al., 2007). This suggests the presence of a feedback loop that informs the cell which DSCAM variant binds to the pathogen’s surface and should thus be preferentially produced through alternative splicing of Dscam pre-mRNA.

Recently, significant progress has been made in understanding the role of Dscam in the immune response in crustaceans, leading to the proposal of a potential feedback mechanism. Activation of macrophage-like hemocytes in the Chinese mitten crab (Eriocheir sinensis) enhances the production and diversification of DSCAM variants in both circulating and membrane-bound forms (Li et al., 2018). DSCAM that can bind to pathogens is subsequently internalized through homodimeric interaction between circulating and membrane-bound forms, activating the adaptor protein Dreadlocks (Dock) (Li and Guan, 2004). Dock physically interacts with and activates various serine/threonine kinases, thus triggering signaling events such as phosphorylation and nuclear translocation of the NFĸB homolog Dorsal, as well as the activation of MAPK-ERK-JNK signaling cascade. These signals lead to increased production of antimicrobial peptides and a shift in the ratio of hnRNP (hrp36) and SR-protein (B52). This shift may stabilize the alternative splicing machinery and limit Dscam splicing to produce only a few preselected DSCAM isoforms (Li et al., 2019). However, it remains unclear if a simple change in the HRP36 and B52 ratio is sufficient for stabilizing Dscam alternative splicing. In Drosophila, genetic manipulation of HRP36 and B52 strongly influences Dscam alternative splicing in the CNS, but it tends to cause the inclusion of multiple multivariant domains from a single exon, resulting in dysfunctional DSCAM (Olson et al., 2007). However, the situation in activated hemocytes may differ significantly from that in the CNS as the variability induced by infection is not developmentally regulated.

In addition to stabilizing splicing, Dscam signaling further activates the a disintegrin and metalloproteinase, which sheds the outer DSCAM domains, enabling cleavage of its cytosolic domain by γ-secretase (Li et al., 2021). The intracellular domain then interacts with importin proteins, which guide it to the nucleus, initiating a program that promotes cell persistence and proliferation (Xia et al., 2024; Ng et al., 2014). The signaling mechanism of the cytosolic tail is not fully understood, and given that eight different variants have been observed in cells, it may be relatively complex. However, whether alternative splicing of the cytosolic domain contributes to immune memory remains unknown. Shedding of the extracellular domain may signal that the cell no longer needs to actively fight the pathogen, and this, coupled with increased persistence and proliferation, could provide a basis for the development and maintenance of immune memory. Although the main components of the described Dscam signaling pathway are known to play roles in the Drosophila CNS (Sachse et al., 2019), their implementation and significance in immune-related processes in insects remain to be addressed.

This brings us to the last stage of immune memory formation, which is the maintenance of preselected DSCAM variants for a secondary encounter with the pathogen. However, experimental data documenting this process are currently lacking, leaving the underlying mechanism open to speculation.

It has already been mentioned that cells expressing preselected DSCAM variants may proliferate, thus increasing their numbers (Xia et al., 2024). Indeed, infection-induced proliferation is commonly observed in many insect species, particularly during larval and pupal stages (Eleftherianos et al., 2021). However, some insect species with well-documented immune memory display limited proliferative potential in immune cells during the adult stage, and no specific hematopoietic organs or niches have been identified as responsible for immune memory maintenance so far (Sanchez Bosch et al., 2019; Ghosh et al., 2015).

An alternative explanation could involve the storage of preselected DSCAM variants in the form of either mRNA or translated proteins. Dscam mRNA might be stored in various membraneless organelles, such as p-bodies, or ω-speckles (Luo et al., 2018), consistent with evidence of numerous RNA-binding proteins interacting with Dscam mRNA in Drosophila. Likewise, preselected DSCAM variants in protein form could accumulate in cytosolic protein granules, bind to the surface membrane of plasmatocytes, or circulate in the hemolymph.

Anchoring DSCAM receptors to the plasmatocyte membrane may increase the immune system’s sensitivity to the pathogen. Recognizing a pathogen and producing preselected, pathogen-binding DSCAM forms could potentially eliminate the infection in its early stages (Figure 6).

Figure 6

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Although Dscam signaling plays a crucial role in pathogen recognition and opsonization, other immune responses, such as phagocytosis, the production of ROS, antimicrobial peptides, and melanization, also contribute to pathogen elimination. However, there is no experimental evidence suggesting that these responses are triggered in a pathogen-specific manner. Consequently, they are unlikely to serve as the primary mechanisms of immune memory formation but may function as important complementary processes. For instance, cytokine-like molecules could act as co-stimulatory factors during immune memory formation.

Understanding the molecular mechanisms of insect innate immune memory could have far-reaching implications, particularly for advancements in immunology, evolutionary biology, biotechnology, and agriculture. Investigating these mechanisms may help trace the evolution of the immune system across invertebrate species. In addition, since insects evolved over 400 million years ago, their ability to ‘remember’ infections without adaptive immunity suggests that innate immune memory is a fundamental trait that predates the evolution of vertebrate adaptive immune system. Unraveling how insects generate immune memory without B and T cells could shed light on the mechanisms of trained immunity in vertebrates. Additionally, it may deepen our understanding of host–pathogen coevolution, potentially uncovering novel strategies pathogens use to evade the host immune response.

The formation of innate immune memory involves epigenetic modifications, such as DNA methylation and histone acetylation, which can persist long after an infection has cleared. Intriguingly, some studies suggest that immune memory can be passed on to offspring, enabling challenged parents to produce progeny with enhanced immune defenses (Gegner et al., 2019). These findings have profound implications for understanding rapid adaptation to environmental pressures, lending support to aspects of Lamarckian evolution, in which acquired traits can be transmitted across generations.

The capacity of vertebrates to develop immune resistance has historically been leveraged in the development of vaccination (Saleh et al., 2021). Vaccination remains one of the most significant breakthroughs in immunology, saving millions of lives each year and helping humanity overcome some of the deadliest and most devastating diseases (Riedel, 2005). The discovery of adaptive immunity in prokaryotes and insects suggests that vaccination principles might also be applicable to these organisms. However, this potential has yet to be thoroughly explored.

Based on the mechanism of insect antiviral immune memory described above, it is reasonable to assume that delivering viral dsRNA to macrophages could be sufficient for immunization. Macrophages have the ability to amplify immune signals and disseminate them to other cells within the organism. This is supported by preliminary experiments and empirical data, showing that injection or feeding of viral nucleic acids alone can provide individuals with a baseline level of acquired immunity against secondary infections (Saleh et al., 2009; Tassetto et al., 2017).

In mosquitoes, both feeding and injection of viral RNA increase resistance to secondary viral infections, with protective effects observed even after injecting as few as 10⁵ copies of viral RNA (Romoli et al., 2024). Efficient prophylaxis has been achieved also against entomopathogenic fungi as injection of lipopolysaccharides prior to Metarhizium anisopliae exposure confers protection in T. molitor (Moret and Siva-Jothy, 2003). An innovative approach has also been developed in honeybees, where improved resistance to viral infections has been documented in individuals fed bacteria heterologously expressing plasmids with viral nucleic acid fragments (Ricigliano et al., 2024). Recently, feeding honeybees with attenuated P. larvae has proven to be an effective treatment against American foulbrood (Dickel et al., 2022). Overall, however, these experiments are relatively rare, and the mechanisms underlying their effects often remain unclear.

Honeybee colonies are currently threatened by the widespread transmission of several viral and bacterial pandemic diseases (Parveen et al., 2022). Protecting bee colonies from these pathogens is therefore a critical issue that vaccination could resolve (Dickel et al., 2022).

On the other hand, blood-feeding insects, especially in tropical areas, transmit a number of diseases that claim millions of victims every year (Belluco et al., 2023). The challenge posed by insect vectors of human diseases lies in their high tolerance to human pathogens. Mosquitoes, ticks, tsetse flies, and fleas do not sufficiently suppress the pathogens they carry, making them not only ideal vectors but also reservoirs for pathogen multiplication. Manipulating the immune tolerance of these vectors to the pathogens they transmit is a currently considered strategy to reduce pathogen spread and, consequently, the incidence of the diseases they cause (Lambrechts and Saleh, 2019).

Over the past few decades, a substantial body of experimental evidence has accumulated, demonstrating that insects possess a form of specific immune memory. However, inconsistencies in experimental design have hindered the interpretation of results and their broader implications. In this review, we outline three types of acquired immunity in insects and highlight key principles to consider when designing experiments on innate immune memory. Although the mechanisms underlying immune memory formation in insects remain largely unknown, significant progress has been made, particularly through studies in Drosophila. This review summarizes current knowledge on the mechanisms of innate immune memory formation and identifies critical unanswered questions for future research. Understanding these mechanisms could be crucial for comparing the molecular basis of acquired immunity across various invertebrates and drawing parallels with immune processes in mammals and other vertebrates. Furthermore, such insights may inform strategies for artificially inducing innate immune memory in crop pollinators or for activating the immune systems of insect vectors against the pathogens they transmit. Such an approach could potentially reduce pathogen spread and, consequently, the incidence of the diseases they cause.

1. 1. Apidianakis Y
   2. Mindrinos MN
   3. Xiao W
   4. Lau GW
   5. Baldini RL
   6. Davis RW
   7. Rahme LG

   (2005) Profiling early infection responses: Pseudomonas aeruginosa eludes host defenses by suppressing antimicrobial peptide gene expression

   PNAS 102:2573–2578.

   https://doi.org/10.1073/pnas.0409588102

   • PubMed
   • Google Scholar
2. 1. Aprelev P
   2. Bruce TF
   3. Beard CE
   4. Adler PH
   5. Kornev KG

   (2019) Nucleation and formation of a primary clot in insect blood

   Scientific Reports 9:3451.

   https://doi.org/10.1038/s41598-019-40129-0

   • PubMed
   • Google Scholar
3. 1. Arch M
   2. Vidal M
   3. Koiffman R
   4. Melkie ST
   5. Cardona PJ

   (2022) Drosophila melanogaster as a model to study innate immune memory

   Frontiers in Microbiology 13:991678.

   https://doi.org/10.3389/fmicb.2022.991678

   • PubMed
   • Google Scholar
4. 1. Bagasra O
   2. Prilliman KR

   (2004) RNA interference: The molecular immune system

   The Histochemical Journal 35:545–553.

   https://doi.org/10.1007/s10735-004-2192-8

   • Google Scholar
5. 1. Bajgar A
   2. Krejčová G
   3. Doležal T

   (2021) Polarization of macrophages in insects: opening gates for immuno-metabolic research

   Frontiers in Cell and Developmental Biology 9:629238.

   https://doi.org/10.3389/fcell.2021.629238

   • PubMed
   • Google Scholar
6. 1. Banerjee U
   2. Girard JR
   3. Goins LM
   4. Spratford CM

   (2019) Drosophila as a genetic model for hematopoiesis

   Genetics 211:367–417.

   https://doi.org/10.1534/genetics.118.300223

   • Google Scholar
7. 1. Belluco S
   2. Bertola M
   3. Montarsi F
   4. Di Martino G
   5. Granato A
   6. Stella R
   7. Martinello M
   8. Bordin F
   9. Mutinelli F

   (2023) Insects and public health: an overview

   Insects 14:240.

   https://doi.org/10.3390/insects14030240

   • PubMed
   • Google Scholar
8. 1. Berkhout B

   (2018) RNAi-mediated antiviral immunity in mammals

   Current Opinion in Virology 32:9–14.

   https://doi.org/10.1016/j.coviro.2018.07.008

   • Google Scholar
9. 1. Bernheim A
   2. Cury J
   3. Poirier EZ

   (2024) The immune modules conserved across the tree of life: towards a definition of ancestral immunity

   PLOS Biology 22:e3002717.

   https://doi.org/10.1371/journal.pbio.3002717

   • PubMed
   • Google Scholar
10. 1. Bilandžija H
    2. Laslo M
    3. Porter ML
    4. Fong DW

    (2017) Melanization in response to wounding is ancestral in arthropods and conserved in albino cave species

    Scientific Reports 7:17148.

    https://doi.org/10.1038/s41598-017-17471-2

    • PubMed
    • Google Scholar
11. 1. Brooks AN
    2. Duff MO
    3. May G
    4. Yang L
    5. Bolisetty M
    6. Landolin J
    7. Wan K
    8. Sandler J
    9. Booth BW
    10. Celniker SE
    11. Graveley BR
    12. Brenner SE

    (2015) Regulation of alternative splicing in Drosophila by 56 RNA binding proteins

    Genome Research 25:1771–1780.

    https://doi.org/10.1101/gr.192518.115

    • PubMed
    • Google Scholar
12. 1. Browne N
    2. Heelan M
    3. Kavanagh K

    (2013) An analysis of the structural and functional similarities of insect hemocytes and mammalian phagocytes

    Virulence 4:597–603.

    https://doi.org/10.4161/viru.25906

    • PubMed
    • Google Scholar
13. 1. Bruner-Montero G
    2. Luque CM
    3. Cesar CS
    4. Ding SD
    5. Day JP
    6. Jiggins FM

    (2023) Hunting Drosophila viruses from wild populations: A novel isolation approach and characterisation of viruses

    PLOS Pathogens 19:e1010883.

    https://doi.org/10.1371/journal.ppat.1010883

    • PubMed
    • Google Scholar
14. 1. Buchon N
    2. Silverman N
    3. Cherry S

    (2014) Immunity in Drosophila melanogaster--from microbial recognition to whole-organism physiology

    Nature Reviews. Immunology 14:796–810.

    https://doi.org/10.1038/nri3763

    • PubMed
    • Google Scholar
15. 1. Cabrera K
    2. Hoard DS
    3. Gibson O
    4. Martinez DI
    5. Wunderlich Z

    (2023) Drosophila immune priming to Enterococcus faecalis relies on immune tolerance rather than resistance

    PLOS Pathogens 19:e1011567.

    https://doi.org/10.1371/journal.ppat.1011567

    • PubMed
    • Google Scholar
16. 1. Celotto AM
    2. Graveley BR

    (2001) Alternative splicing of the Drosophila Dscam pre-mRNA is both temporally and spatially regulated

    Genetics 159:599–608.

    https://doi.org/10.1093/genetics/159.2.599

    • PubMed
    • Google Scholar
17. 1. Cheng T
    2. Lin P
    3. Huang L
    4. Wu Y
    5. Jin S
    6. Liu C
    7. Xia Q

    (2016) Genome-wide analysis of host responses to four different types of microorganisms in bombyx mori (Lepidoptera: Bombycidae)

    Journal of Insect Science 16:69.

    https://doi.org/10.1093/jisesa/iew020

    • PubMed
    • Google Scholar
18. 1. Christofi T
    2. Apidianakis Y

    (2013) Drosophila immune priming against Pseudomonas aeruginosa is short-lasting and depends on cellular and humoral immunity

    F1000Research 2:76.

    https://doi.org/10.12688/f1000research.2-76.v1

    • PubMed
    • Google Scholar
19. 1. Cole EL
    2. Empringham JS
    3. Biro C
    4. Thompson GJ
    5. Rosengaus RB

    (2020) Relish as a candidate marker for transgenerational immune priming in a dampwood termite (Blattodae: Archeotermopsidae)

    Insects 11:149.

    https://doi.org/10.3390/insects11030149

    • PubMed
    • Google Scholar
20. 1. Contreras-Garduño J
    2. Rodríguez MC
    3. Hernández-Martínez S
    4. Martínez-Barnetche J
    5. Alvarado-Delgado A
    6. Izquierdo J
    7. Herrera-Ortiz A
    8. Moreno-García M
    9. Velazquez-Meza ME
    10. Valverde V
    11. Argotte-Ramos R
    12. Rodríguez MH
    13. Lanz-Mendoza H

    (2015) Plasmodium berghei induced priming in Anopheles albimanus independently of bacterial co-infection

    Developmental and Comparative Immunology 52:172–181.

    https://doi.org/10.1016/j.dci.2015.05.004

    • PubMed
    • Google Scholar
21. 1. Cooper D
    2. Eleftherianos I

    (2017) Memory and specificity in the insect immune system: current perspectives and future challenges

    Frontiers in Immunology 8:539.

    https://doi.org/10.3389/fimmu.2017.00539

    • PubMed
    • Google Scholar
22. 1. Decout A
    2. Katz JD
    3. Venkatraman S
    4. Ablasser A

    (2021) The cGAS–STING pathway as a therapeutic target in inflammatory diseases

    Nature Reviews. Immunology 21:548–569.

    https://doi.org/10.1038/s41577-021-00524-z

    • Google Scholar
23. 1. Dho M
    2. Candian V
    3. Tedeschi R

    (2023) Insect antimicrobial peptides: advancements, enhancements and new challenges

    Antibiotics 12:952.

    https://doi.org/10.3390/antibiotics12060952

    • PubMed
    • Google Scholar
24. 1. Dickel F
    2. Bos NMP
    3. Hughes H
    4. Martín-Hernández R
    5. Higes M
    6. Kleiser A
    7. Freitak D

    (2022) The oral vaccination with Paenibacillus larvae bacterin can decrease susceptibility to American Foulbrood infection in honey bees-A safety and efficacy study

    Frontiers in Veterinary Science 9:946237.

    https://doi.org/10.3389/fvets.2022.946237

    • PubMed
    • Google Scholar
25. 1. Divangahi M
    2. Aaby P
    3. Khader SA
    4. Barreiro LB
    5. Bekkering S
    6. Chavakis T
    7. van Crevel R
    8. Curtis N
    9. DiNardo AR
    10. Dominguez-Andres J
    11. Duivenvoorden R
    12. Fanucchi S
    13. Fayad Z
    14. Fuchs E
    15. Hamon M
    16. Jeffrey KL
    17. Khan N
    18. Joosten LAB
    19. Kaufmann E
    20. Latz E
    21. Matarese G
    22. van der Meer JWM
    23. Mhlanga M
    24. Mulder WJM
    25. Naik S
    26. Novakovic B
    27. O’Neill L
    28. Ochando J
    29. Ozato K
    30. Riksen NP
    31. Sauerwein R
    32. Sherwood ER
    33. Schlitzer A
    34. Schultze JL
    35. Sieweke MH
    36. Benn CS
    37. Stunnenberg H
    38. Sun J
    39. van de Veerdonk FL
    40. Weis S
    41. Williams DL
    42. Xavier R
    43. Netea MG

    (2021) Trained immunity, tolerance, priming and differentiation: distinct immunological processes

    Nature Immunology 22:2–6.

    https://doi.org/10.1038/s41590-020-00845-6

    • PubMed
    • Google Scholar
26. 1. Dong Y
    2. Taylor HE
    3. Dimopoulos G

    (2006) AgDscam, a hypervariable immunoglobulin domain-containing receptor of the Anopheles gambiae innate immune system

    PLOS Biology 4:e229.

    https://doi.org/10.1371/journal.pbio.0040229

    • PubMed
    • Google Scholar
27. 1. Dubuffet A
    2. Zanchi C
    3. Boutet G
    4. Moreau J
    5. Teixeira M
    6. Moret Y

    (2015) Trans-generational immune priming protects the eggs only against gram-positive bacteria in the mealworm beetle

    PLOS Pathogens 11:e1005178.

    https://doi.org/10.1371/journal.ppat.1005178

    • PubMed
    • Google Scholar
28. 1. Duffy JB

    (2002) GAL4 system in Drosophila: A fly geneticist’s swiss army knife

    Genesis 34:1–15.

    https://doi.org/10.1002/gene.10150

    • Google Scholar
29. 1. Eaglesham JB
    2. Kranzusch PJ

    (2024) Tracing the evolutionary origins of antiviral immunity

    PLOS Biology 22:e3002481.

    https://doi.org/10.1371/journal.pbio.3002481

    • PubMed
    • Google Scholar
30. 1. Eggert H
    2. Kurtz J
    3. Diddens-de Buhr MF

    (2014) Different effects of paternal trans-generational immune priming on survival and immunity in step and genetic offspring

    Proceedings of the Royal Society B 281:20142089.

    https://doi.org/10.1098/rspb.2014.2089

    • Google Scholar
31. 1. Eleftherianos I
    2. Heryanto C
    3. Bassal T
    4. Zhang W
    5. Tettamanti G
    6. Mohamed A

    (2021) Haemocyte-mediated immunity in insects: Cells, processes and associated components in the fight against pathogens and parasites

    Immunology 164:401–432.

    https://doi.org/10.1111/imm.13390

    • PubMed
    • Google Scholar
32. 1. El Safadi D
    2. Mokhtari A
    3. Krejbich M
    4. Lagrave A
    5. Hirigoyen U
    6. Lebeau G
    7. Viranaicken W
    8. Krejbich-Trotot P

    (2024) Exosome-mediated antigen delivery: unveiling novel strategies in viral infection control and vaccine design

    Vaccines 12:12030280.

    https://doi.org/10.3390/vaccines12030280

    • PubMed
    • Google Scholar
33. 1. Evans CJ
    2. Hartenstein V
    3. Banerjee U

    (2003) Thicker than blood

    Developmental Cell 5:673–690.

    https://doi.org/10.1016/S1534-5807(03)00335-6

    • Google Scholar
34. 1. Faulhaber LM
    2. Karp RD

    (1992)

    A diphasic immune response against bacteria in the American cockroach

    Immunology 75:378–381.

    • PubMed
    • Google Scholar
35. Book

    1. Federici BA

    (2009) Pathogens of Insects in Encyclopedia of Insects

    Academic Press.

    https://doi.org/10.1016/B978-0-12-374144-8.00202-2

    • Google Scholar
36. 1. Fisher JJ
    2. Hajek AE

    (2015) Maternal exposure of a beetle to pathogens protects offspring against fungal disease

    PLOS ONE 10:e0125197.

    https://doi.org/10.1371/journal.pone.0125197

    • PubMed
    • Google Scholar
37. 1. Freitak D
    2. Heckel DG
    3. Vogel H

    (2009) Dietary-dependent trans-generational immune priming in an insect herbivore

    Proceedings of the Royal Society B 276:2617–2624.

    https://doi.org/10.1098/rspb.2009.0323

    • Google Scholar
38. 1. Freitak D
    2. Schmidtberg H
    3. Dickel F
    4. Lochnit G
    5. Vogel H
    6. Vilcinskas A

    (2014) The maternal transfer of bacteria can mediate trans-generational immune priming in insects

    Virulence 5:547–554.

    https://doi.org/10.4161/viru.28367

    • PubMed
    • Google Scholar
39. 1. Fries I
    2. Lindstrom A
    3. Korpela S

    (2006) Vertical transmission of American foulbrood (Paenibacillus larvae) in honey bees (Apis mellifera)

    Veterinary Microbiology 114:269–274.

    https://doi.org/10.1016/j.vetmic.2005.11.068

    • Google Scholar
40. 1. Futo M
    2. Armitage SAO
    3. Kurtz J

    (2015) Microbiota plays a role in oral immune priming in tribolium castaneum

    Frontiers in Microbiology 6:01383.

    https://doi.org/10.3389/fmicb.2015.01383

    • PubMed
    • Google Scholar
41. 1. Futo M
    2. Sell MP
    3. Kutzer MAM
    4. Kurtz J

    (2017) Specificity of oral immune priming in the red flour beetle Tribolium castaneum

    Biology Letters 13:20170632.

    https://doi.org/10.1098/rsbl.2017.0632

    • Google Scholar
42. 1. Gálvez D
    2. Chapuisat M

    (2014) Immune priming and pathogen resistance in ant queens

    Ecology and Evolution 4:1761–1767.

    https://doi.org/10.1002/ece3.1070

    • PubMed
    • Google Scholar
43. 1. Gammon DB
    2. Mello CC

    (2015) RNA interference-mediated antiviral defense in insects

    Current Opinion in Insect Science 8:111–120.

    https://doi.org/10.1016/j.cois.2015.01.006

    • PubMed
    • Google Scholar
44. 1. Gegner J
    2. Baudach A
    3. Mukherjee K
    4. Halitschke R
    5. Vogel H
    6. Vilcinskas A

    (2019) Epigenetic mechanisms are involved in sex-specific trans-generational immune priming in the Lepidopteran model host Manduca sexta

    Frontiers in Physiology 10:137.

    https://doi.org/10.3389/fphys.2019.00137

    • PubMed
    • Google Scholar
45. 1. Genersch E

    (2010) American Foulbrood in honeybees and its causative agent, Paenibacillus larvae

    Journal of Invertebrate Pathology 103:S10–S19.

    https://doi.org/10.1016/j.jip.2009.06.015

    • PubMed
    • Google Scholar
46. 1. Ghosh S
    2. Singh A
    3. Mandal S
    4. Mandal L

    (2015) Active hematopoietic hubs in Drosophila adults generate hemocytes and contribute to immune response

    Developmental Cell 33:478–488.

    https://doi.org/10.1016/j.devcel.2015.03.014

    • PubMed
    • Google Scholar
47. 1. Gilbert C
    2. Belliardo C

    (2022) The diversity of endogenous viral elements in insects

    Current Opinion in Insect Science 49:48–55.

    https://doi.org/10.1016/j.cois.2021.11.007

    • Google Scholar
48. 1. Gomes FM
    2. Silva M
    3. Molina-Cruz A
    4. Barillas-Mury C

    (2022) Molecular mechanisms of insect immune memory and pathogen transmission

    PLOS Pathogens 18:e1010939.

    https://doi.org/10.1371/journal.ppat.1010939

    • PubMed
    • Google Scholar
49. 1. González-tokman DM
    2. González-santoyo I
    3. Lanz-mendoza H
    4. Córdoba Aguilar A

    (2010) Territorial damselflies do not show immunological priming in the wild

    Physiological Entomology 35:364–372.

    https://doi.org/10.1111/j.1365-3032.2010.00752.x

    • Google Scholar
50. 1. Goto A
    2. Okado K
    3. Martins N
    4. Cai H
    5. Barbier V
    6. Lamiable O
    7. Troxler L
    8. Santiago E
    9. Kuhn L
    10. Paik D
    11. Silverman N
    12. Holleufer A
    13. Hartmann R
    14. Liu J
    15. Peng T
    16. Hoffmann JA
    17. Meignin C
    18. Daeffler L
    19. Imler J-L

    (2018) The kinase IKKβ regulates a STING- and NF-κB-Dependent antiviral response pathway in Drosophila

    Immunity 49:225–234.

    https://doi.org/10.1016/j.immuni.2018.07.013

    • PubMed
    • Google Scholar
51. 1. Graveley BR

    (2005) Mutually exclusive splicing of the insect Dscam pre-mRNA directed by competing intronic RNA secondary structures

    Cell 123:65–73.

    https://doi.org/10.1016/j.cell.2005.07.028

    • PubMed
    • Google Scholar
52. 1. Hamilton C
    2. Lejeune BT
    3. Rosengaus RB

    (2011) Trophallaxis and prophylaxis: social immunity in the carpenter ant Camponotus pennsylvanicus

    Biology Letters 7:89–92.

    https://doi.org/10.1098/rsbl.2010.0466

    • PubMed
    • Google Scholar
53. 1. Hattori D
    2. Demir E
    3. Kim HW
    4. Viragh E
    5. Zipursky SL
    6. Dickson BJ

    (2007) Dscam diversity is essential for neuronal wiring and self-recognition

    Nature 449:223–227.

    https://doi.org/10.1038/nature06099

    • PubMed
    • Google Scholar
54. 1. Hernández López J
    2. Schuehly W
    3. Crailsheim K
    4. Riessberger-Gallé U

    (2014) Trans-generational immune priming in honeybees

    Proceedings of the Royal Society B 281:20140454.

    https://doi.org/10.1098/rspb.2014.0454

    • Google Scholar
55. 1. Hille F
    2. Richter H
    3. Wong SP
    4. Bratovič M
    5. Ressel S
    6. Charpentier E

    (2018) The Biology of CRISPR-Cas: backward and forward

    Cell 172:1239–1259.

    https://doi.org/10.1016/j.cell.2017.11.032

    • Google Scholar
56. 1. Huang S
    2. Tao X
    3. Yuan S
    4. Zhang Y
    5. Li P
    6. Beilinson HA
    7. Zhang Y
    8. Yu W
    9. Pontarotti P
    10. Escriva H
    11. Le Petillon Y
    12. Liu X
    13. Chen S
    14. Schatz DG
    15. Xu A

    (2016) Discovery of an Active RAG transposon illuminates the origins of V(D)J recombination

    Cell 166:102–114.

    https://doi.org/10.1016/j.cell.2016.05.032

    • PubMed
    • Google Scholar
57. 1. Hultmark D
    2. Borge-Renberg K

    (2007) Drosophila immunity: is antigen processing the first step?

    Current Biology 17:R22–R24.

    https://doi.org/10.1016/j.cub.2006.11.039

    • Google Scholar
58. 1. Jiang F
    2. Doudna JA

    (2017) CRISPR–Cas9 structures and mechanisms

    Annual Review of Biophysics 46:505–529.

    https://doi.org/10.1146/annurev-biophys-062215-010822

    • Google Scholar
59. 1. Johnson PLF
    2. Kochin BF
    3. Ahmed R
    4. Antia R

    (2012) How do antigenically varying pathogens avoid cross-reactive responses to invariant antigens?

    Proceedings of the Royal Society B 279:2777–2785.

    https://doi.org/10.1098/rspb.2012.0005

    • Google Scholar
60. Book

    1. Kanost MR
    2. Zhao L

    (1996) Insect Hemolymph Proteins from the Ig Superfamily

    Springer.

    https://doi.org/10.1007/978-3-642-79693-7_7

    • Google Scholar
61. 1. Kato Y
    2. Motoi Y
    3. Taniai K
    4. Kadono-Okuda K
    5. Yamamoto M
    6. Higashino Y
    7. Shimabukuro M
    8. Chowdhury S
    9. Xu J
    10. Sugiyama M

    (1994) Lipopolysaccharide-lipophorin complex formation in insect hemolymph: a common pathway of lipopolysaccharide detoxification both in insects and in mammals

    Insect Biochemistry and Molecular Biology 24:547–555.

    https://doi.org/10.1016/0965-1748(94)90090-6

    • PubMed
    • Google Scholar
62. 1. Kaufman J

    (2018) Unfinished business: evolution of the MHC and the adaptive immune system of jawed vertebrates

    Annual Review of Immunology 36:383–409.

    https://doi.org/10.1146/annurev-immunol-051116-052450

    • PubMed
    • Google Scholar
63. 1. Kingsolver MB
    2. Huang Z
    3. Hardy RW

    (2013) Insect antiviral innate immunity: pathways, effectors, and connections

    Journal of Molecular Biology 425:4921–4936.

    https://doi.org/10.1016/j.jmb.2013.10.006

    • Google Scholar
64. 1. Knorr E
    2. Schmidtberg H
    3. Arslan D
    4. Bingsohn L
    5. Vilcinskas A

    (2015) Translocation of bacteria from the gut to the eggs triggers maternal transgenerational immune priming in Tribolium castaneum

    Biology Letters 11:20150885.

    https://doi.org/10.1098/rsbl.2015.0885

    • PubMed
    • Google Scholar
65. 1. Konrad M
    2. Vyleta ML
    3. Theis FJ
    4. Stock M
    5. Tragust S
    6. Klatt M
    7. Drescher V
    8. Marr C
    9. Ugelvig LV
    10. Cremer S

    (2012) Social transfer of pathogenic fungus promotes active immunisation in ant colonies

    PLOS Biology 10:e1001300.

    https://doi.org/10.1371/journal.pbio.1001300

    • PubMed
    • Google Scholar
66. 1. Koonin EV
    2. Krupovic M

    (2015) Evolution of adaptive immunity from transposable elements combined with innate immune systems

    Nature Reviews. Genetics 16:184–192.

    https://doi.org/10.1038/nrg3859

    • Google Scholar
67. 1. Kreahling JM
    2. Graveley BR

    (2005) The iStem, a long-range RNA secondary structure element required for efficient exon inclusion in the Drosophila Dscam pre-mRNA

    Molecular and Cellular Biology 25:10251–10260.

    https://doi.org/10.1128/MCB.25.23.10251-10260.2005

    • PubMed
    • Google Scholar
68. 1. Krejčová G
    2. Danielová A
    3. Nedbalová P
    4. Kazek M
    5. Strych L
    6. Chawla G
    7. Tennessen JM
    8. Lieskovská J
    9. Jindra M
    10. Doležal T
    11. Bajgar A

    (2019) Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense

    eLife 8:e50414.

    https://doi.org/10.7554/eLife.50414

    • PubMed
    • Google Scholar
69. 1. Krejčová G
    2. Morgantini C
    3. Zemanová H
    4. Lauschke VM
    5. Kovářová J
    6. Kubásek J
    7. Nedbalová P
    8. Kamps-Hughes N
    9. Moos M
    10. Aouadi M
    11. Doležal T
    12. Bajgar A

    (2023) Macrophage-derived insulin antagonist ImpL2 induces lipoprotein mobilization upon bacterial infection

    The EMBO Journal 42:e114086.

    https://doi.org/10.15252/embj.2023114086

    • PubMed
    • Google Scholar
70. 1. Kurtz J
    2. Franz K

    (2003) Innate defence: evidence for memory in invertebrate immunity

    Nature 425:37–38.

    https://doi.org/10.1038/425037a

    • PubMed
    • Google Scholar
71. 1. Lambrechts L
    2. Saleh MC

    (2019) Manipulating mosquito tolerance for arbovirus control

    Cell Host & Microbe 26:309–313.

    https://doi.org/10.1016/j.chom.2019.08.005

    • PubMed
    • Google Scholar
72. 1. Leggewie M
    2. Schnettler E

    (2018) RNAi-mediated antiviral immunity in insects and their possible application

    Current Opinion in Virology 32:108–114.

    https://doi.org/10.1016/j.coviro.2018.10.004

    • PubMed
    • Google Scholar
73. 1. Li W
    2. Guan KL

    (2004) The Down syndrome cell adhesion molecule (DSCAM) interacts with and activates Pak

    The Journal of Biological Chemistry 279:32824–32831.

    https://doi.org/10.1074/jbc.M401878200

    • PubMed
    • Google Scholar
74. 1. Li XJ
    2. Yang L
    3. Li D
    4. Zhu YT
    5. Wang Q
    6. Li WW

    (2018) Pathogen-specific binding soluble down syndrome cell adhesion molecule (Dscam) Regulates Phagocytosis via Membrane-Bound Dscam in crab

    Frontiers in Immunology 9:801.

    https://doi.org/10.3389/fimmu.2018.00801

    • PubMed
    • Google Scholar
75. 1. Li D
    2. Wan Z
    3. Li X
    4. Duan M
    5. Yang L
    6. Ruan Z
    7. Wang Q
    8. Li W

    (2019) Alternatively spliced down syndrome cell adhesion molecule (Dscam) controls innate immunity in crab

    Journal of Biological Chemistry 294:16440–16450.

    https://doi.org/10.1074/jbc.RA119.010247

    • Google Scholar
76. 1. Li W

    (2021) Dscam in arthropod immune priming: What is known and what remains unknown

    Developmental and Comparative Immunology 125:104231.

    https://doi.org/10.1016/j.dci.2021.104231

    • PubMed
    • Google Scholar
77. 1. Li H
    2. Jin XK
    3. Zhou KM
    4. Zhao H
    5. Zhao YH
    6. Wang Q
    7. Li WW

    (2021) Down syndrome cell adhesion molecule triggers membrane-to-nucleus signaling-regulated hemocyte proliferation against bacterial infection in invertebrates

    Journal of Immunology 207:2265–2277.

    https://doi.org/10.4049/jimmunol.2100575

    • PubMed
    • Google Scholar
78. 1. Lindenbergh MFS
    2. Stoorvogel W

    (2018) Antigen presentation by extracellular vesicles from professional antigen-presenting cells

    Annual Review of Immunology 36:435–459.

    https://doi.org/10.1146/annurev-immunol-041015-055700

    • PubMed
    • Google Scholar
79. 1. Linder JE
    2. Promislow DEL

    (2009) Cross-generational fitness effects of infection in Drosophila melanogaster

    Fly 3:143–150.

    https://doi.org/10.4161/fly.8051

    • PubMed
    • Google Scholar
80. 1. Little TJ
    2. Hultmark D
    3. Read AF

    (2005) Invertebrate immunity and the limits of mechanistic immunology

    Nature Immunology 6:651–654.

    https://doi.org/10.1038/ni1219

    • PubMed
    • Google Scholar
81. 1. Liu H
    2. Pizzano S
    3. Li R
    4. Zhao W
    5. Veling MW
    6. Hu Y
    7. Yang L
    8. Ye B

    (2020) isoTarget: a genetic method for analyzing the functional diversity of splicing isoforms in Vivo

    Cell Reports 33:108361.

    https://doi.org/10.1016/j.celrep.2020.108361

    • Google Scholar
82. 1. Longdon B
    2. Cao C
    3. Martinez J
    4. Jiggins FM

    (2013) Previous exposure to an RNA virus does not protect against subsequent infection in Drosophila melanogaster

    PLOS ONE 8:e73833.

    https://doi.org/10.1371/journal.pone.0073833

    • PubMed
    • Google Scholar
83. 1. Luo Y
    2. Na Z
    3. Slavoff SA

    (2018) P-Bodies: composition, properties, and functions

    Biochemistry 57:2424–2431.

    https://doi.org/10.1021/acs.biochem.7b01162

    • Google Scholar
84. 1. Ma G
    2. Roberts H
    3. Sarjan M
    4. Featherstone N
    5. Lahnstein J
    6. Akhurst R
    7. Schmidt O

    (2005) Is the mature endotoxin Cry1Ac from Bacillus thuringiensis inactivated by a coagulation reaction in the gut lumen of resistant Helicoverpa armigera larvae?

    Insect Biochemistry and Molecular Biology 35:729–739.

    https://doi.org/10.1016/j.ibmb.2005.02.011

    • Google Scholar
85. 1. Mahanta DK
    2. Bhoi TK
    3. Komal J
    4. Samal I
    5. Nikhil RM
    6. Paschapur AU
    7. Singh G
    8. Kumar PVD
    9. Desai HR
    10. Ahmad MA
    11. Singh PP
    12. Majhi PK
    13. Mukherjee U
    14. Singh P
    15. Saini V
    16. Srinivasa N
    17. Yele Y
    18. Shahanaz S

    (2023) Insect-pathogen crosstalk and the cellular-molecular mechanisms of insect immunity: uncovering the underlying signaling pathways and immune regulatory function of non-coding RNAs

    Frontiers in Immunology 14:1169152.

    https://doi.org/10.3389/fimmu.2023.1169152

    • PubMed
    • Google Scholar
86. 1. Mahbubur Rahman M
    2. Roberts HLS
    3. Schmidt O

    (2007) Tolerance to Bacillus thuringiensis endotoxin in immune-suppressed larvae of the flour moth Ephestia kuehniella

    Journal of Invertebrate Pathology 96:125–132.

    https://doi.org/10.1016/j.jip.2007.03.018

    • Google Scholar
87. 1. Mayo-Muñoz D
    2. Pinilla-Redondo R
    3. Birkholz N
    4. Fineran PC

    (2023) A host of armor: Prokaryotic immune strategies against mobile genetic elements

    Cell Reports 42:112672.

    https://doi.org/10.1016/j.celrep.2023.112672

    • PubMed
    • Google Scholar
88. 1. McClure CD
    2. Hassan A
    3. Aughey GN
    4. Butt K
    5. Estacio-Gómez A
    6. Duggal A
    7. Ying Sia C
    8. Barber AF
    9. Southall TD

    (2022) An auxin-inducible, GAL4-compatible, gene expression system for Drosophila

    eLife 11:e67598.

    https://doi.org/10.7554/eLife.67598

    • PubMed
    • Google Scholar
89. 1. McManus CJ
    2. Graveley BR

    (2011) RNA structure and the mechanisms of alternative splicing

    Current Opinion in Genetics & Development 21:373–379.

    https://doi.org/10.1016/j.gde.2011.04.001

    • PubMed
    • Google Scholar
90. 1. McNamara KB
    2. van Lieshout E
    3. Simmons LW

    (2014) The effect of maternal and paternal immune challenge on offspring immunity and reproduction in a cricket

    Journal of Evolutionary Biology 27:1020–1028.

    https://doi.org/10.1111/jeb.12376

    • PubMed
    • Google Scholar
91. 1. Meijers R
    2. Puettmann-Holgado R
    3. Skiniotis G
    4. Liu J
    5. Walz T
    6. Wang J
    7. Schmucker D

    (2007) Structural basis of Dscam isoform specificity

    Nature 449:487–491.

    https://doi.org/10.1038/nature06147

    • PubMed
    • Google Scholar
92. 1. Melcarne C
    2. Lemaitre B
    3. Kurant E

    (2019) Phagocytosis in Drosophila: From molecules and cellular machinery to physiology

    Insect Biochemistry and Molecular Biology 109:1–12.

    https://doi.org/10.1016/j.ibmb.2019.04.002

    • PubMed
    • Google Scholar
93. 1. Miyashita A
    2. Takahashi S
    3. Ishii K
    4. Sekimizu K
    5. Kaito C

    (2015) Primed immune responses triggered by ingested bacteria lead to systemic infection tolerance in silkworms

    PLOS ONE 10:e0130486.

    https://doi.org/10.1371/journal.pone.0130486

    • PubMed
    • Google Scholar
94. 1. Mondotte JA
    2. Gausson V
    3. Frangeul L
    4. Blanc H
    5. Lambrechts L
    6. Saleh MC

    (2018) Immune priming and clearance of orally acquired RNA viruses in Drosophila

    Nature Microbiology 3:1394–1403.

    https://doi.org/10.1038/s41564-018-0265-9

    • Google Scholar
95. 1. Mondotte JA
    2. Gausson V
    3. Frangeul L
    4. Suzuki Y
    5. Vazeille M
    6. Mongelli V
    7. Blanc H
    8. Failloux A-B
    9. Saleh M-C

    (2020) Evidence for long-lasting transgenerational antiviral immunity in insects

    Cell Reports 33:108506.

    https://doi.org/10.1016/j.celrep.2020.108506

    • PubMed
    • Google Scholar
96. 1. Moreau J
    2. Martinaud G
    3. Troussard J
    4. Zanchi C
    5. Moret Y

    (2012) Trans‐generational immune priming is constrained by the maternal immune response in an insect

    Oikos 121:1828–1832.

    https://doi.org/10.1111/j.1600-0706.2011.19933.x

    • Google Scholar
97. 1. Moreno-García M
    2. Vargas V
    3. Ramírez-Bello I
    4. Hernández-Martínez G
    5. Lanz-Mendoza H

    (2015) Bacterial exposure at the larval stage induced sexual immune dimorphism and priming in adult aedes aegypti mosquitoes

    PLOS ONE 10:e0133240.

    https://doi.org/10.1371/journal.pone.0133240

    • Google Scholar
98. 1. Moret Y
    2. Siva-Jothy MT

    (2003) Adaptive innate immunity? Responsive-mode prophylaxis in the mealworm beetle, Tenebrio molitor

    Proceedings of the Royal Society of London. Series B 270:2475–2480.

    https://doi.org/10.1098/rspb.2003.2511

    • Google Scholar
99. 1. Müller V
    2. de Boer RJ
    3. Bonhoeffer S
    4. Szathmáry E

    (2018) An evolutionary perspective on the systems of adaptive immunity

    Biological Reviews of the Cambridge Philosophical Society 93:505–528.

    https://doi.org/10.1111/brv.12355

    • PubMed
    • Google Scholar
100. Book

     1. Nakhleh J
     2. Moussawi LE
     3. Osta MA

     (2017) The melanization response in insect immunity

     In: Ligoxygakis P, editors. Advances in Insect Physiology. Academic Press. pp. 83–109.

     https://doi.org/10.1016/bs.aiip.2016.11.002

     • Google Scholar
101. 1. Nascimento MTC
     2. Silva KP
     3. Garcia MCF
     4. Medeiros MN
     5. Machado EA
     6. Nascimento SB
     7. Saraiva EM

     (2018) DNA extracellular traps are part of the immune repertoire of Periplaneta americana

     Developmental and Comparative Immunology 84:62–70.

     https://doi.org/10.1016/j.dci.2018.01.012

     • PubMed
     • Google Scholar
102. 1. Netea MG
     2. Schlitzer A
     3. Placek K
     4. Joosten LAB
     5. Schultze JL

     (2019) Innate and adaptive immune memory: an evolutionary continuum in the host’s response to pathogens

     Cell Host & Microbe 25:13–26.

     https://doi.org/10.1016/j.chom.2018.12.006

     • PubMed
     • Google Scholar
103. 1. Newsom S
     2. Parameshwaran HP
     3. Martin L
     4. Rajan R

     (2020) The CRISPR-cas mechanism for adaptive immunity and alternate bacterial functions fuels diverse biotechnologies

     Frontiers in Cellular and Infection Microbiology 10:619763.

     https://doi.org/10.3389/fcimb.2020.619763

     • PubMed
     • Google Scholar
104. 1. Ng TH
     2. Chiang YA
     3. Yeh YC
     4. Wang HC

     (2014) Review of Dscam-mediated immunity in shrimp and other arthropods

     Developmental and Comparative Immunology 46:129–138.

     https://doi.org/10.1016/j.dci.2014.04.002

     • PubMed
     • Google Scholar
105. 1. Ng TH
     2. Kurtz J

     (2020) Dscam in immunity: A question of diversity in insects and crustaceans

     Developmental & Comparative Immunology 105:103539.

     https://doi.org/10.1016/j.dci.2019.103539

     • Google Scholar
106. 1. Olson S
     2. Blanchette M
     3. Park J
     4. Savva Y
     5. Yeo GW
     6. Yeakley JM
     7. Rio DC
     8. Graveley BR

     (2007) A regulator of Dscam mutually exclusive splicing fidelity

     Nature Structural & Molecular Biology 14:1134–1140.

     https://doi.org/10.1038/nsmb1339

     • PubMed
     • Google Scholar
107. 1. Ortmann B
     2. Copeman J
     3. Lehner PJ
     4. Sadasivan B
     5. Herberg JA
     6. Grandea AG
     7. Riddell SR
     8. Tampé R
     9. Spies T
     10. Trowsdale J
     11. Cresswell P

     (1997) A critical role for tapasin in the assembly and function of multimeric MHC class I-TAP complexes

     Science 277:1306–1309.

     https://doi.org/10.1126/science.277.5330.1306

     • PubMed
     • Google Scholar
108. 1. Palmieri B
     2. Vadala’ M
     3. Palmieri L

     (2021) Immune memory: an evolutionary perspective

     Human Vaccines & Immunotherapeutics 17:1604–1606.

     https://doi.org/10.1080/21645515.2020.1846396

     • PubMed
     • Google Scholar
109. 1. Parveen N
     2. Miglani R
     3. Kumar A
     4. Dewali S
     5. Kumar K
     6. Sharma N
     7. Bisht SS

     (2022) Honey bee pathogenesis posing threat to its global population: a short review

     Proceedings of the Indian National Science Academy 88:11–32.

     https://doi.org/10.1007/s43538-022-00062-9

     • Google Scholar
110. 1. Patel NF
     2. Oliver SV

     (2024) Generation of specific immune memory by bacterial exposure in the major malaria vector Anopheles arabiensis (Diptera: Culicidae)

     Current Research in Insect Science 5:100085.

     https://doi.org/10.1016/j.cris.2024.100085

     • PubMed
     • Google Scholar
111. 1. Pereira SB
     2. de Mattos DP
     3. Gonzalez MS
     4. Mello CB
     5. Azambuja P
     6. de Castro DP
     7. Vieira CS

     (2024) Immune signaling pathways in Rhodnius prolixus in the context of Trypanosoma rangeli infection: cellular and humoral immune responses and microbiota modulation

     Frontiers in Physiology 15:1435447.

     https://doi.org/10.3389/fphys.2024.1435447

     • PubMed
     • Google Scholar
112. 1. Pham LN
     2. Dionne MS
     3. Shirasu-Hiza M
     4. Schneider DS

     (2007) A specific primed immune response in Drosophila is dependent on phagocytes

     PLOS Pathogens 3:e26.

     https://doi.org/10.1371/journal.ppat.0030026

     • PubMed
     • Google Scholar
113. 1. Prakash A
     2. Khan I

     (2022) Why do insects evolve immune priming? A search for crossroads

     Developmental and Comparative Immunology 126:104246.

     https://doi.org/10.1016/j.dci.2021.104246

     • PubMed
     • Google Scholar
114. 1. Rahman MM
     2. Roberts HLS
     3. Sarjan M
     4. Asgari S
     5. Schmidt O

     (2004) Induction and transmission of Bacillus thuringiensis tolerance in the flour moth Ephestia kuehniella

     PNAS 101:2696–2699.

     https://doi.org/10.1073/pnas.0306669101

     • Google Scholar
115. 1. Rajan A
     2. Perrimon N

     (2011) Drosophila as a model for interorgan communication: lessons from studies on energy homeostasis

     Developmental Cell 21:29–31.

     https://doi.org/10.1016/j.devcel.2011.06.034

     • PubMed
     • Google Scholar
116. 1. Ramirez JL
     2. de Almeida Oliveira G
     3. Calvo E
     4. Dalli J
     5. Colas RA
     6. Serhan CN
     7. Ribeiro JM
     8. Barillas-Mury C

     (2015) A mosquito lipoxin/lipocalin complex mediates innate immune priming in Anopheles gambiae

     Nature Communications 6:7403.

     https://doi.org/10.1038/ncomms8403

     • PubMed
     • Google Scholar
117. 1. Rath D
     2. Amlinger L
     3. Rath A
     4. Lundgren M

     (2015) The CRISPR-Cas immune system: Biology, mechanisms and applications

     Biochimie 117:119–128.

     https://doi.org/10.1016/j.biochi.2015.03.025

     • Google Scholar
118. 1. Reber A
     2. Chapuisat M

     (2012) No evidence for immune priming in ants exposed to a fungal pathogen

     PLOS ONE 7:e35372.

     https://doi.org/10.1371/journal.pone.0035372

     • PubMed
     • Google Scholar
119. 1. Ricigliano VA
     2. McMenamin A
     3. Martin Ewert A
     4. Adjaye D
     5. Simone-Finstrom M
     6. Rainey VP

     (2024) Green biomanufacturing of edible antiviral therapeutics for managed pollinators

     Npj Sustainable Agriculture 2:000117.

     https://doi.org/10.1038/s44264-024-00011-7

     • Google Scholar
120. 1. Riedel S

     (2005) Edward jenner and the history of smallpox and vaccination

     Baylor University Medical Center Proceedings 18:21–25.

     https://doi.org/10.1080/08998280.2005.11928028

     • Google Scholar
121. 1. Riessberger-Gallé U
     2. Hernández López J
     3. Schuehly W
     4. Crockett S
     5. Krainer S
     6. Crailsheim K

     (2015) Immune responses of honeybees and their fitness costs as compared to bumblebees

     Apidologie 46:238–249.

     https://doi.org/10.1007/s13592-014-0318-x

     • Google Scholar
122. 1. Rimer J
     2. Cohen IR
     3. Friedman N

     (2014) Do all creatures possess an acquired immune system of some sort?

     BioEssays 36:273–281.

     https://doi.org/10.1002/bies.201300124

     • PubMed
     • Google Scholar
123. 1. Rodrigues J
     2. Brayner FA
     3. Alves LC
     4. Dixit R
     5. Barillas-Mury C

     (2010) Hemocyte differentiation mediates innate immune memory in Anopheles gambiae mosquitoes

     Science 329:1353–1355.

     https://doi.org/10.1126/science.1190689

     • PubMed
     • Google Scholar
124. 1. Rodriguez-Andres J
     2. Axford J
     3. Hoffmann A
     4. Fazakerley J

     (2024) Mosquito transgenerational antiviral immunity is mediated by vertical transfer of virus DNA sequences and RNAi

     iScience 27:108598.

     https://doi.org/10.1016/j.isci.2023.108598

     • PubMed
     • Google Scholar
125. 1. Romoli O
     2. Henrion-Lacritick A
     3. Blanc H
     4. Frangeul L
     5. Saleh MC

     (2024) Limitations in harnessing oral RNA interference as an antiviral strategy in Aedes aegypti

     iScience 27:109261.

     https://doi.org/10.1016/j.isci.2024.109261

     • PubMed
     • Google Scholar
126. 1. Rosengaus RB
     2. Traniello JFA
     3. Chen T
     4. Brown JJ
     5. Karp RD

     (1999) Immunity in a social insect

     Naturwissenschaften 86:588–591.

     https://doi.org/10.1007/s001140050679

     • Google Scholar
127. 1. Rosengaus RB
     2. Malak T
     3. Mackintosh C

     (2013) Immune-priming in ant larvae: social immunity does not undermine individual immunity

     Biology Letters 9:20130563.

     https://doi.org/10.1098/rsbl.2013.0563

     • PubMed
     • Google Scholar
128. 1. Roth O
     2. Sadd BM
     3. Schmid-Hempel P
     4. Kurtz J

     (2009) Strain-specific priming of resistance in the red flour beetle, Tribolium castaneum

     Proceedings of the Royal Society B 276:145–151.

     https://doi.org/10.1098/rspb.2008.1157

     • Google Scholar
129. 1. Roth O
     2. Joop G
     3. Eggert H
     4. Hilbert J
     5. Daniel J
     6. Schmid-Hempel P
     7. Kurtz J

     (2010) Paternally derived immune priming for offspring in the red flour beetle, Tribolium castaneum

     The Journal of Animal Ecology 79:403–413.

     https://doi.org/10.1111/j.1365-2656.2009.01617.x

     • PubMed
     • Google Scholar
130. 1. Roy M
     2. Viginier B
     3. Saint-Michel É
     4. Arnaud F
     5. Ratinier M
     6. Fablet M

     (2020) Viral infection impacts transposable element transcript amounts in Drosophila

     PNAS 117:12249–12257.

     https://doi.org/10.1073/pnas.2006106117

     • Google Scholar
131. 1. Sabin LR
     2. Hanna SL
     3. Cherry S

     (2010) Innate antiviral immunity in Drosophila

     Current Opinion in Immunology 22:4–9.

     https://doi.org/10.1016/j.coi.2010.01.007

     • PubMed
     • Google Scholar
132. 1. Sachse SM
     2. Lievens S
     3. Ribeiro LF
     4. Dascenco D
     5. Masschaele D
     6. Horré K
     7. Misbaer A
     8. Vanderroost N
     9. De Smet AS
     10. Salta E
     11. Erfurth M-L
     12. Kise Y
     13. Nebel S
     14. Van Delm W
     15. Plaisance S
     16. Tavernier J
     17. De Strooper B
     18. De Wit J
     19. Schmucker D

     (2019) Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation

     The EMBO Journal 38:e99669.

     https://doi.org/10.15252/embj.201899669

     • PubMed
     • Google Scholar
133. 1. Sadd BM
     2. Schmid-Hempel P

     (2006) Insect immunity shows specificity in protection upon secondary pathogen exposure

     Current Biology 16:1206–1210.

     https://doi.org/10.1016/j.cub.2006.04.047

     • PubMed
     • Google Scholar
134. 1. Sadd BM
     2. Schmid-Hempel P

     (2007) Facultative but persistent trans-generational immunity via the mother’s eggs in bumblebees

     Current Biology 17:R1046–R1047.

     https://doi.org/10.1016/j.cub.2007.11.007

     • PubMed
     • Google Scholar
135. 1. Saleh M-C
     2. Tassetto M
     3. van Rij RP
     4. Goic B
     5. Gausson V
     6. Berry B
     7. Jacquier C
     8. Antoniewski C
     9. Andino R

     (2009) Antiviral immunity in Drosophila requires systemic RNA interference spread

     Nature 458:346–350.

     https://doi.org/10.1038/nature07712

     • PubMed
     • Google Scholar
136. 1. Saleh A
     2. Qamar S
     3. Tekin A
     4. Singh R
     5. Kashyap R

     (2021) Vaccine development throughout history

     Cureus 13:16635.

     https://doi.org/10.7759/cureus.16635

     • Google Scholar
137. 1. Salmela H
     2. Amdam GV
     3. Freitak D

     (2015) Transfer of immunity from mother to offspring is mediated via egg-yolk protein vitellogenin

     PLOS Pathogens 11:e1005015.

     https://doi.org/10.1371/journal.ppat.1005015

     • PubMed
     • Google Scholar
138. 1. Sanchez Bosch P
     2. Makhijani K
     3. Herboso L
     4. Gold KS
     5. Baginsky R
     6. Woodcock KJ
     7. Alexander B
     8. Kukar K
     9. Corcoran S
     10. Jacobs T
     11. Ouyang D
     12. Wong C
     13. Ramond EJV
     14. Rhiner C
     15. Moreno E
     16. Lemaitre B
     17. Geissmann F
     18. Brückner K

     (2019) Adult Drosophila lack hematopoiesis but rely on a blood cell reservoir at the respiratory epithelia to relay infection signals to surrounding tissues

     Developmental Cell 51:787–803.

     https://doi.org/10.1016/j.devcel.2019.10.017

     • Google Scholar
139. 1. Schmucker D
     2. Clemens JC
     3. Shu H
     4. Worby CA
     5. Xiao J
     6. Muda M
     7. Dixon JE
     8. Zipursky SL

     (2000) Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity

     Cell 101:671–684.

     https://doi.org/10.1016/s0092-8674(00)80878-8

     • PubMed
     • Google Scholar
140. 1. Schmucker D
     2. Chen B

     (2009) DSCAM and DSCAM: complex genes in simple animals, complex animals yet simple genes

     Genes & Development 23:147–156.

     https://doi.org/10.1101/gad.1752909

     • PubMed
     • Google Scholar
141. 1. Schneider DS

     (2021) Immunology’s intolerance of disease tolerance

     Nature Reviews. Immunology 21:624–625.

     https://doi.org/10.1038/s41577-021-00619-7

     • PubMed
     • Google Scholar
142. 1. Schwarz RS
     2. Evans JD

     (2013) Single and mixed-species trypanosome and microsporidia infections elicit distinct, ephemeral cellular and humoral immune responses in honey bees

     Developmental and Comparative Immunology 40:300–310.

     https://doi.org/10.1016/j.dci.2013.03.010

     • PubMed
     • Google Scholar
143. 1. Skirmuntt EC
     2. Escalera-Zamudio M
     3. Teeling EC
     4. Smith A
     5. Katzourakis A

     (2020) The potential role of endogenous viral elements in the evolution of bats as reservoirs for zoonotic viruses

     Annual Review of Virology 7:103–119.

     https://doi.org/10.1146/annurev-virology-092818-015613

     • PubMed
     • Google Scholar
144. 1. Smith VL
     2. Cheng Y
     3. Bryant BR
     4. Schorey JS

     (2017) Exosomes function in antigen presentation during an in vivo Mycobacterium tuberculosis infection

     Scientific Reports 7:43578.

     https://doi.org/10.1038/srep43578

     • PubMed
     • Google Scholar
145. 1. St Leger RJ

     (2021) Insects and their pathogens in a changing climate

     Journal of Invertebrate Pathology 184:107644.

     https://doi.org/10.1016/j.jip.2021.107644

     • PubMed
     • Google Scholar
146. 1. Stork NE

     (2018) How many species of insects and other terrestrial arthropods are there on earth?

     Annual Review of Entomology 63:31–45.

     https://doi.org/10.1146/annurev-ento-020117-043348

     • PubMed
     • Google Scholar
147. 1. Taengchaiyaphum S
     2. Buathongkam P
     3. Sukthaworn S
     4. Wongkhaluang P
     5. Sritunyalucksana K
     6. Flegel TW

     (2021) Shrimp parvovirus circular DNA fragments arise from both endogenous viral elements and the infecting virus

     Frontiers in Immunology 12:729528.

     https://doi.org/10.3389/fimmu.2021.729528

     • PubMed
     • Google Scholar
148. 1. Tafesh-Edwards G
     2. Eleftherianos I

     (2020) Drosophila immunity against natural and nonnatural viral pathogens

     Virology 540:165–171.

     https://doi.org/10.1016/j.virol.2019.12.001

     • PubMed
     • Google Scholar
149. 1. Tanaka T
     2. Yano T
     3. Usuki S
     4. Seo Y
     5. Mizuta K
     6. Okaguchi M
     7. Yamaguchi M
     8. Hanyu-Nakamura K
     9. Toyama-Sorimachi N
     10. Brückner K
     11. Nakamura A

     (2024) Endocytosed dsRNAs induce lysosomal membrane permeabilization that allows cytosolic dsRNA translocation for Drosophila RNAi responses

     Nature Communications 15:6993.

     https://doi.org/10.1038/s41467-024-51343-4

     • PubMed
     • Google Scholar
150. 1. Tang H

     (2009) Regulation and function of the melanization reaction in Drosophila

     Fly 3:105–111.

     https://doi.org/10.4161/fly.3.1.7747

     • PubMed
     • Google Scholar
151. 1. Tang C
     2. Kurata S
     3. Fuse N

     (2023) Re-recognition of innate immune memory as an integrated multidimensional concept

     Microbiology and Immunology 67:355–364.

     https://doi.org/10.1111/1348-0421.13083

     • PubMed
     • Google Scholar
152. 1. Tassetto M
     2. Kunitomi M
     3. Andino R

     (2017) Circulating immune cells mediate a systemic RNAi-based adaptive antiviral response in Drosophila

     Cell 169:314–325.

     https://doi.org/10.1016/j.cell.2017.03.033

     • PubMed
     • Google Scholar
153. 1. Tassetto M
     2. Kunitomi M
     3. Whitfield ZJ
     4. Dolan PT
     5. Sánchez-Vargas I
     6. Garcia-Knight M
     7. Ribiero I
     8. Chen T
     9. Olson KE
     10. Andino R

     (2019) Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements

     eLife 8:e41244.

     https://doi.org/10.7554/eLife.41244

     • PubMed
     • Google Scholar
154. 1. Tate AT
     2. Graham AL

     (2015) Trans‐generational priming of resistance in wild flour beetles reflects the primed phenotypes of laboratory populations and is inhibited by co‐infection with a common parasite

     Functional Ecology 29:1059–1069.

     https://doi.org/10.1111/1365-2435.12411

     • Google Scholar
155. 1. Thomas AM
     2. Rudolf VHW

     (2010) Challenges of metamorphosis in invertebrate hosts: maintaining parasite resistance across life‐history stages

     Ecological Entomology 35:200–205.

     https://doi.org/10.1111/j.1365-2311.2009.01169.x

     • Google Scholar
156. 1. Tidbury HJ
     2. Pedersen AB
     3. Boots M

     (2011) Within and transgenerational immune priming in an insect to a DNA virus

     Proceedings of the Royal Society B 278:871–876.

     https://doi.org/10.1098/rspb.2010.1517

     • Google Scholar
157. 1. Tolwinski N

     (2017) Introduction: Drosophila—a model system for developmental biology

     Journal of Developmental Biology 5:5030009.

     https://doi.org/10.3390/jdb5030009

     • Google Scholar
158. 1. Trammell CE
     2. Goodman AG

     (2021) Host factors that control mosquito-borne viral infections in humans and their vector

     Viruses 13:748.

     https://doi.org/10.3390/v13050748

     • PubMed
     • Google Scholar
159. 1. Trauer U
     2. Hilker M

     (2013) Parental legacy in insects: variation of transgenerational immune priming during offspring development

     PLOS ONE 8:e63392.

     https://doi.org/10.1371/journal.pone.0063392

     • PubMed
     • Google Scholar
160. 1. Trauer-Kizilelma U
     2. Hilker M

     (2015) Impact of transgenerational immune priming on the defence of insect eggs against parasitism

     Developmental and Comparative Immunology 51:126–133.

     https://doi.org/10.1016/j.dci.2015.03.004

     • PubMed
     • Google Scholar
161. 1. Ustaoglu P
     2. Haussmann IU
     3. Liao H
     4. Torres-Mendez A
     5. Arnold R
     6. Irimia M
     7. Soller M

     (2019) Srrm234, but not canonical SR and hnRNP proteins, drive inclusion of Dscam exon 9 variable exons

     RNA 25:1353–1365.

     https://doi.org/10.1261/rna.071316.119

     • PubMed
     • Google Scholar
162. 1. van Rij RP
     2. Saleh M-C
     3. Berry B
     4. Foo C
     5. Houk A
     6. Antoniewski C
     7. Andino R

     (2006) The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster

     Genes & Development 20:2985–2995.

     https://doi.org/10.1101/gad.1482006

     • Google Scholar
163. 1. Vargas V
     2. Cime-Castillo J
     3. Lanz-Mendoza H

     (2020) Immune priming with inactive dengue virus during the larval stage of Aedes aegypti protects against the infection in adult mosquitoes

     Scientific Reports 10:6723.

     https://doi.org/10.1038/s41598-020-63402-z

     • PubMed
     • Google Scholar
164. 1. Vorburger C
     2. Gegenschatz SE
     3. Ranieri G
     4. Rodriguez P

     (2008) Limited scope for maternal effects in aphid defence against parasitoids

     Ecological Entomology 33:189–196.

     https://doi.org/10.1111/j.1365-2311.2007.00949.x

     • Google Scholar
165. 1. Vuscan P
     2. Kischkel B
     3. Joosten LAB
     4. Netea MG

     (2024) Trained immunity: General and emerging concepts

     Immunological Reviews 323:164–185.

     https://doi.org/10.1111/imr.13326

     • PubMed
     • Google Scholar
166. 1. Wan Z
     2. Nan X
     3. Zhuo Y
     4. Xia H
     5. Li W

     (2023) Alternatively spliced exon 33 in Dscam controls antibacterial responses through regulating cellular endocytosis and regulation of actin cytoskeleton gene expression in the hemocytes of the Chinese mitten crab (Eriocheir sinensis)

     Developmental and Comparative Immunology 140:104619.

     https://doi.org/10.1016/j.dci.2022.104619

     • PubMed
     • Google Scholar
167. 1. Wang Q
     2. Liu Y
     3. He HJ
     4. Zhao XF
     5. Wang JX

     (2010) Immune responses of Helicoverpa armigera to different kinds of pathogens

     BMC Immunology 11:9.

     https://doi.org/10.1186/1471-2172-11-9

     • PubMed
     • Google Scholar
168. 1. Wang X
     2. Li G
     3. Yang Y
     4. Wang W
     5. Zhang W
     6. Pan H
     7. Zhang P
     8. Yue Y
     9. Lin H
     10. Liu B
     11. Bi J
     12. Shi F
     13. Mao J
     14. Meng Y
     15. Zhan L
     16. Jin Y

     (2012) An RNA architectural locus control region involved in Dscam mutually exclusive splicing

     Nature Communications 3:1255.

     https://doi.org/10.1038/ncomms2269

     • PubMed
     • Google Scholar
169. 1. Wang JY
     2. Pausch P
     3. Doudna JA

     (2022) Structural biology of CRISPR–Cas immunity and genome editing enzymes

     Nature Reviews. Microbiology 20:641–656.

     https://doi.org/10.1038/s41579-022-00739-4

     • Google Scholar
170. 1. Wang H
     2. Chen Q
     3. Wei T

     (2024) Complex interactions among insect viruses-insect vector-arboviruses

     Insect Science 31:683–693.

     https://doi.org/10.1111/1744-7917.13285

     • PubMed
     • Google Scholar
171. 1. Wang J
     2. Li Y

     (2024) Current advances in antiviral RNA interference in mammals

     The FEBS Journal 291:208–216.

     https://doi.org/10.1111/febs.16728

     • Google Scholar
172. 1. Watson FL
     2. Püttmann-Holgado R
     3. Thomas F
     4. Lamar DL
     5. Hughes M
     6. Kondo M
     7. Rebel VI
     8. Schmucker D

     (2005) Extensive diversity of Ig-superfamily proteins in the immune system of insects

     Science 309:1874–1878.

     https://doi.org/10.1126/science.1116887

     • PubMed
     • Google Scholar
173. 1. Wein T
     2. Sorek R

     (2022) Bacterial origins of human cell-autonomous innate immune mechanisms

     Nature Reviews. Immunology 22:629–638.

     https://doi.org/10.1038/s41577-022-00705-4

     • PubMed
     • Google Scholar
174. 1. Wojtowicz WM
     2. Flanagan JJ
     3. Millard SS
     4. Zipursky SL
     5. Clemens JC

     (2004) Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding

     Cell 118:619–633.

     https://doi.org/10.1016/j.cell.2004.08.021

     • PubMed
     • Google Scholar
175. 1. Wojtowicz WM
     2. Wu W
     3. Andre I
     4. Qian B
     5. Baker D
     6. Zipursky SL

     (2007) A vast repertoire of Dscam binding specificities arises from modular interactions of variable Ig domains

     Cell 130:1134–1145.

     https://doi.org/10.1016/j.cell.2007.08.026

     • PubMed
     • Google Scholar
176. 1. Wu G
     2. Li M
     3. Liu Y
     4. Ding Y
     5. Yi Y

     (2015a) The specificity of immune priming in silkworm, Bombyx mori, is mediated by the phagocytic ability of granular cells

     Journal of Insect Physiology 81:60–68.

     https://doi.org/10.1016/j.jinsphys.2015.07.004

     • PubMed
     • Google Scholar
177. 1. Wu G
     2. Yi Y
     3. Lv Y
     4. Li M
     5. Wang J
     6. Qiu L

     (2015b) The lipopolysaccharide (LPS) of Photorhabdus luminescens TT01 can elicit dose- and time-dependent immune priming in Galleria mellonella larvae

     Journal of Invertebrate Pathology 127:63–72.

     https://doi.org/10.1016/j.jip.2015.03.007

     • PubMed
     • Google Scholar
178. 1. Wu G
     2. Yi Y
     3. Sun J
     4. Li M
     5. Qiu L

     (2015c) No evidence for priming response in Galleria mellonella larvae exposed to toxin protein PirA2B2 from Photorhabdus luminescens TT01: An association with the inhibition of the host cellular immunity

     Vaccine 33:6307–6313.

     https://doi.org/10.1016/j.vaccine.2015.09.046

     • Google Scholar
179. 1. Xia HH
     2. Zhu LM
     3. Shen LT
     4. Wan ZC

     (2024) Cytoplasmic tail of transmembrane dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes of Chinese mitten crab (Eriocheir sinensis)

     Fish & Shellfish Immunology 151:109626.

     https://doi.org/10.1016/j.fsi.2024.109626

     • PubMed
     • Google Scholar
180. 1. Zanchi C
     2. Troussard JP
     3. Martinaud G
     4. Moreau J
     5. Moret Y

     (2011) Differential expression and costs between maternally and paternally derived immune priming for offspring in an insect

     The Journal of Animal Ecology 80:1174–1183.

     https://doi.org/10.1111/j.1365-2656.2011.01872.x

     • PubMed
     • Google Scholar
181. 1. Zhang W
     2. Tettamanti G
     3. Bassal T
     4. Heryanto C
     5. Eleftherianos I
     6. Mohamed A

     (2021) Regulators and signalling in insect antimicrobial innate immunity: functional molecules and cellular pathways

     Cellular Signalling 83:110003.

     https://doi.org/10.1016/j.cellsig.2021.110003

     • PubMed
     • Google Scholar
182. 1. Zhang Y
     2. Dai Y
     3. Wang J
     4. Xu Y
     5. Li Z
     6. Lu J
     7. Xu Y
     8. Zhong J
     9. Ding S-W
     10. Li Y

     (2022) Mouse circulating extracellular vesicles contain virus-derived siRNAs active in antiviral immunity

     The EMBO Journal 41:e109902.

     https://doi.org/10.15252/embj.2021109902

     • PubMed
     • Google Scholar

Author details

1. Gabriela Krejčová

   Department of Molecular Biology and Genetics, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic

   Contribution

   Conceptualization, Supervision, Validation, Visualization, Writing – original draft, Project administration, Writing – review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-4648-973X

2. Adam Bajgar

   Department of Molecular Biology and Genetics, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic

   Contribution

   Conceptualization, Resources, Supervision, Funding acquisition, Validation, Visualization, Writing – original draft, Project administration, Writing – review and editing

   For correspondence

   bajgaa00@prf.jcu.cz

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-9721-7534

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