There is a huge international effort to combat malaria, but even today almost half a million people die from the disease each year, mostly young children in Africa. Malaria infections are caused by the parasite Plasmodium, which is spread by mosquitoes. The Fulani are an ethnic group of people from West Africa that are naturally better at fighting malaria infections with the most dangerous form of the parasite, Plasmodium falciparum. Fulani show fewer symptoms of malaria and carry fewer parasites when they are infected. They also have fewer cases of sickle cell disease, a condition that is known to protect against malaria. Yet, no one understands what it is that makes Fulani more resistant to malaria than other people, such as people of other ethnic groups that live in the same region of West Africa but who do not intermarry with the Fulani.

Past studies that looked at likely genes, such as those involved in the immune response, could not find any differences between the Fulani and people who have a normal susceptibility to malaria. Quin, Bujila et al. performed a pilot study to look at the activity of all the genes in immune cells from Fulani people who had become naturally infected with P. falciparum to see which genes are switched on or off after an infection. If some genes are used differently in the Fulani compared to other ethnic groups, then it is likely that these genes are responsible for the Fulani’s more effective immune response to P. falciparum.

First, Quin, Bujila et al. looked for chemical markers that are naturally added to DNA to influence the activity of nearby genes, and used other methods to determine which genes are switched on and at what level. Unexpectedly, for those markers looked at, no difference was found between the ethnic groups investigated. However, the other experiments did show that in a certain type of immune cell in the Fulani over 1,000 genes become notably more active, or less active, after P. falciparum infection. These cells, called monocytes, are important for the immune system’s first line of defence, which begins the attack against an infection and alerts the rest of the immune system. Lastly, inflammation is a common part of the body’s immune response to many parasites. When Quin, Bujila et al. measured the level of inflammatory molecules, they found that Fulani have higher levels of molecules that promote inflammation than other ethnic groups.

Together these results suggest that a group of genes in the monocytes of Fulani are set in a ‘primed’ state, which helps monocytes to drive the fight against P. falciparum more effectively. The cause for the heightened primed state remains unclear, but previous studies looking into bacterial and fungal infections have shown early infections can prime the immune system to promote more inflammation during a second infection. These new findings suggest that such processes might also occur for malaria infections, and so might represent a new avenue of research in the quest for better treatments for malaria.

The Fulani ethnic group has relatively better protection from Plasmodium falciparum malaria than other ethnic groups living alongside them in West Africa. Since the first report of the different response of Fulani to P.falciparum in 1996 (Modiano et al., 1996), populations of Fulani living sympatrically with other ethnic groups from Mali to as far east as Sudan, have consistently been reported to have fewer symptomatic cases of malaria, lower P.falciparum infection rates, and lower P.falciparum density in infected individuals (Arama et al., 2015a). However, the basis for the lower susceptibility of Fulani to malaria is yet to be established.

Malaria has been a major selective force on the human genome in endemic areas, and a number of factors conferring reduced susceptibility to malaria have been described, such as enzymatic G6PD deficiency, or abnormal hemoglobins - the most well know of which, HbS, confers sickle cell disease (Allison, 2009). However, the incidence of these classic malaria resistance genes are lower in the Fulani than in other sympatric ethnic populations (Modiano et al., 2001; Mangano et al., 2015), and therefore cannot account for their better protection. Neither have targeted SNP analysis of candidate genes involved in the immune response to malaria been able to explain the observed difference in Fulani susceptibility to P.falciparum (Arama et al., 2015a). Studies examining specific characteristics of the immune response to malaria in Fulani have shown a number of differences – Fulani are more responsive to P.falciparum antigens, with higher levels of P.falciparum specific IgG1-3, IgE and IgM antibodies (Modiano et al., 1996; Arama et al., 2015a; Arama et al., 2015b; Bolad et al., 2005; Vafa et al., 2009; Boström et al., 2012; Cherif et al., 2012; Maiga et al., 2014; Cherif et al., 2015; Cherif et al., 2016); Fulani have a higher ratio of pro-inflammatory to anti-inflammatory cytokines (Boström et al., 2012; McCall et al., 2010; Arama et al., 2011; Farouk et al., 2005); Fulani have a different proportion of specific immune cells, including more activated memory B-cells (Portugal et al., 2012), fewer circulating regulatory T-cells (McCall et al., 2010; Torcia et al., 2008), and increased activation of dendritic cells correlating with their lower frequency in circulating blood (Arama et al., 2011). However, no direct associations have been established between these differences and reduced parasite rates in Fulani individuals. Thus, the contribution of differences in immune response in the Fulani to protection from malaria is unclear, as is their underlying cause.

To shed light on the mechanisms that confer the lower susceptibility of Fulani to P.falciparum malaria, we have performed a pilot study examining global DNA methylation and transcription regulation in the Fulani, compared to the Mossi sympatric ethnic group. We have examined both CD14+ (monocyte) and CD14- (predominantly lymphocyte) populations of peripheral blood mononuclear cells from the same individuals, either uninfected or infected with P.falciparum. Our results show that Fulani monocytes, specifically, are more transcriptionally reactive to P.falciparum infection. This is not related to differences in DNA-methylation. Rather, several genes involved in chromatin remodelling and epigenetic regulation of gene expression in immune cell lineages are differentially expressed, indicating that the underlying cause is a change in the chromatin landscape. The heightened transcriptional response is associated with differential expression of a variety of genes involved in the innate immune response, and corresponds with more inflammatory baseline characteristics, and a more activated inflammasome upon P.falciparum infection, in Fulani individuals.

This is a pilot study of adolescent men from Bakoundouba (Burkina Faso), where the Fulani live in sympatry with the Mossi ethnic group (Modiano et al., 1996; Lulli et al., 2009). Due to the 2014 West African Ebola outbreak and local political unrest, the collection was delayed until the end of the July-October high transmission season, to November 2014. All individuals (56) were analysed for P.falciparum infection by PCR, in which other Plasmodium infections were also detected. The baseline characteristics presented in Figure 1a show that the Fulani population had a significantly lower rate of P.falciparum infection (Figure 1b), and significantly higher levels of P.falciparum specific antibodies (IgG) (Figure 1c), consistent with previous reports (Boström et al., 2012; Arama et al., 2011; Perdijk et al., 2013). After having excluded samples with mixed Plasmodium infections, G6PD-deficiency, or hemoglobin C, samples of CD14⁺ (monocytes) and CD14^– (~98% lymphocytes) cells from infected and uninfected Fulani and Mossi individuals were selected for RNA-sequencing and DNA-methylation analyses (Figure 1—figure supplement 1). Samples were selected from the same individuals for each of the the different analyses. Samples from the remaining individuals formed a separate cohort for validation experiments.

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RNA-sequencing analysis of monocytes from uninfected Fulani (n = 7) compared to uninfected Mossi (n = 4) identified 17 significantly differentially expressed (DE) genes (Figure 2a). Analysis by qRT-PCR of a subset of these genes in the validation cohort revealed similar changes in expression, indicating that our results reflected the larger Fulani population (Figure 2b). The most significantly DE gene was P2RX 7 (Figure 2c), encoding P2X purinoceptor 7, a purinergic receptor for ATP that acts as a ligand-gated ion channel (Wiley et al., 2011). P2RX7 is highly expressed in immune cells, particularly monocytes, and its activation drives the formation of the inflammasome and subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18 (Sharma and Kanneganti, 2016). DNA methylation analysis of monocytes from the Mossi and the Fulani revealed only a few sites that were significantly differentially methylated (Supplementary file 1A). These sites did not overlap with the DE genes identified by RNA-sequencing. No DE genes were identified in the CD14^– cells from uninfected Fulani and Mossi.

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We next analysed the transcriptional response of monocytes to P.falciparum infection (Supplementary file 2A and Figure 2—figure supplements 1 and 2). A striking difference between Fulani and Mossi was observed in infected compared to uninfected monocytes: infected Fulani had 1239 DE genes, most of which were downregulated (1095/1239) (Figure 2d and f, Supplementary file 2B); in comparison, infected Mossi had only three DE genes (Figure 2e and f, Supplementary file 2C). The CD14^– fraction from the same individuals did not display differences in gene expression (Figure 2g and h).

The most significantly DE genes in monocytes of infected Fulani are involved in a variety of processes, including immune response, metabolism, cell cycle, chromatin and transcription regulation, RNA metabolism, translation, and ribosomal biogenesis (Figure 3a). Next we examined whether the response was quantitatively (ie different changes in level of expression of the same gene sets) or qualitatively (ie changes in the level of expression of different gene sets) between Fulani and Mossi following infection. Only a few genes were significantly differentially expressed between the two infected populations, suggesting that the majority of significantly DE genes in Fulani also experienced less significant changes in expression in Mossi. (Figure 3—figure supplement 1 and Supplementary file 2D). This indicates that Fulani monocytes have a stronger transcriptional response.

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Figure 3—source data 1

qRT-PCR analysis of selected DE genes in monocytes of validation cohort of Mossi –P.fal (n = 4), Fulani –P.fal (n = 10), Mossi +P.fal (n = 8) and Fulani +P.fal (n = 5) (mean ±SD).

https://doi.org/10.7554/eLife.29156.011

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The DE genes related to immune response include NF-κB regulation, MAPK regulation, AP-1 regulation, inflammasome activation, glytolytic metabolism, migration and vesicle function, and other genes involved in innate immune responses (Figure 3a). Analysis by qRT-PCR of the expression of a subset of genes in monocytes of individuals from the validation cohort showed a similar downregulation in expression as observed in the RNA-sequencing data (Figure 3b and c, Figure 3—source data 1). The qRT-PCR results also indicate that these transcript were present at higher levels in monocytes from uninfected Fulani than Mossi (Figure 3d). Thus, Fulani monocytes have a more transcriptionally active baseline, and express these genes at relatively high levels prior to infection with P.falciparum.

Previous studies have reported that the Fulani have a higher ratio of pro-inflammatory to anti-inflammatory cytokines (Boström et al., 2012; McCall et al., 2010; Torcia et al., 2008; Perdijk et al., 2013), and in agreement with this the levels of the pro-inflammatory IFN-γ were higher, and the levels of the anti-inflammatory TGF-β were lower, in blood plasma from uninfected Fulani than uninfected Mossi in our study (Figure 3e and f). However, in individuals that were infected with P.falciparum, the levels of pro-inflammatory IFNγ and IL-6 were increased in the Mossi but reduced in the Fulani (Figure 3f). While studies have shown higher overall levels of IFNγ in Fulani (Boström et al., 2012; McCall et al., 2010; Torcia et al., 2008), the reduction of IFNγ or other pro-inflammatory cytokines in Fulani upon infection has not been previously reported. Interestingly, the changes in the levels of these cytokines mirrors the expression of the immune response genes above. Collectively, these results indicate monocytes of uninfected Fulani are more immune reactive, driving different dynamics of response upon P.falciparum infection.

Many of the DE genes in monocytes from infected Fulani are involved in the function of the inflammasome (Supplementary file 2E). The inflammasome is a cytoplasmic complex responsible for processing and activation of pro-inflammatory cytokines IL-1β and IL-18, and causing an inflammatory form of cell death - pyroptosis - via processing and activation of gasdermin D (Guo et al., 2015). Monocytes from infected Fulani had significantly reduced expression of inflammasome pathway components (for example the gene encoding gasdermin D, GSDMD, and inflammasome complex scaffold proteins, NLRP12 [Ataide et al., 2014] and NLRC5 [Davis et al., 2011]). Therefore, we investigated the activation of the inflammasome by analyzing levels of its targets, IL-1β and IL-18, in blood plasma. IL-1β was only detected in infected Fulani, and IL-18 was detected at higher levels in infected than uninfected Fulani, whereas the levels in the Mossi did not change (Figure 3g). This indicates that the inflammasome was significantly more activated in infected Fulani than in the Mossi. As the levels of IL-1β and IL-18 are relatively low in blood plasma, we examined the levels of suppressors of inflammasome signaling, including IL-1 receptor antagonist (IL-1Ra), the soluble decoy IL-1 receptor, type II (IL-1RII), and decoy receptor IL-18 binding protein (IL-18BP), which have effective concentrations several orders of magnitude higher their target cytokines (Boraschi and Tagliabue, 2013). These showed similar results, with higher levels in infected Fulani (Figure 3—figure supplement 2; IL-1Ra **p=0.0048, and IL-18BPa *p=0.0149, in infected compared to uninfected Fulani). Interestingly, this is in contrast to levels of other pro-inflammatory cytokines, IFNγ and IL-6, which are higher in uninfected than infected Fulani. Our results suggest that the Fulani respond with a more active inflammasome, which results in feedback inhibition of the expression of inflammasome pathway components.

Analysis of transcription factor binding sites at the most significantly DE genes showed enrichment for ETS family transcription factors, which are downstream regulators of the MAPK and PI3K signalling pathways (Yordy and Muise-Helmericks, 2000). A number of MAPK and PI3K pathway components were differentially expressed, as was the ETS family transcription factor ERG. Significantly DE genes were also enriched in transcription factor binding sites for NF-κB and NRF2, signalling pathways that are directly regulated in activation of innate immune response pathways in monocytes (Dev et al., 2011; Kobayashi et al., 2013). A number of NF-κB regulatory components, as well as the NRF2 binding partner MAFK, were also differentially expressed. Many of these transcription factors are associated with coactivators, responsible for histone modification and altered chromatin accessibility (Martens et al., 2012; Saeed et al., 2012) (Supplementary file 2F).

In addition to genes directly associated with innate immune response, genes involved in inducing different chromatin states and RNA metabolism were differentially expressed in monocytes from infected Fulani (Figure 4a). This suggests that monocytes from the Fulani have a capacity to remodel the chromatin landscape, which could result in a different or stronger transcriptional responses. Several important genes encoding for chromatin and epigenetic factors are differentially regulated. For example PRDM5, which is expressed in heamatapoietic stem cells where it is predicted to regulate chromatin organisation via association with architectural proteins CTCF, Cohesin, and TFIIIC (Riddell et al., 2014; Galli et al., 2013), was upregulated in monocytes of infected Fulani. Several chromatin remodelling components and histone modifying enzymes related to a more open chromatin state were differentially expressed; in particular components of the the SWI/SNF complexes, which are important for transcription of many immune genes and the phase shift to the adaptation phase in B-cells and T-cells (Foster et al., 2007; Schultze, 2017), and components of histone methyl transferase complexes SET1 and MLL complexes, both H3K4-me3 methyl transferases important in haematopoiesis (Yang and Ernst, 2017). Genes encoding enzymes responsible for inducing a silent state, such as SUV39H1, SUV420H1 and HDACs, were also differentially expressed, indicating that the chromatin response to P.falciparum is complex. The downregulation of many of these factors in infected Fulani were confirmed in the validation cohort Figure 4b and c, Figure 4—source data 1). Similar to the immune genes above, genes that are upregulated in response to P.falciparum infection in Mossi, are already expressed at higher levels in uninfected Fulani. The observed differences in expression in monocytes of the Fulani was not caused by DNA-methylation; the DNA methylation was very stable, with few differences between all analysed sample groups (Figure 4—figure supplement 1). The few genes differentially methylated in monocytes from infected and uninfected Fulani did not correspond to the DE genes (Figure 4d, Supplementary files 1B). Further analysis of DE genes in monocytes of infected Fulani, examining their chromosomal position, showed that they cluster in regions (Figure 4e). These regions displayed few differences in DNA methylation (Figure 4g). This suggests that a changed chromatin landscape underlies the altered gene expression pattern.

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Figure 4—source data 1

qRT-PCR analysis of selected DE chromatin regulation genes in monocytes of validation cohort of Mossi –P.fal (n = 4), Fulani –P.fal (n = 10), Mossi +P.fal (n = 8) and Fulani +P.fal (n = 5) (mean ±SD).

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In this pilot study, we have established that monocytes from the Fulani are strikingly more transcriptionally reactive than a sympatric ethnic group in response to infection with P.falciparum. Interestingly, most genes exhibited a lower expression level in infected compared to uninfected monocytes. We speculate that this, seen at the end of the malaria transmission season, is due to one, or both, of the following scenarios: First, the higher levels of transcription of immune response genes in uninfected Fulani may drive a more immediate response following P.falciparum infection, and thus a more rapid and evident return to homeostatic levels of transcription; Second, an acute hyper-active response following P.falciparum infection may result in an subsequent hypo-active state. This is supported by our results showing that genes involved in pathways which are rapidly activated under inflammatory conditions are significantly downregulated in infected Fulani, for example genes encoding aerobic glycolytic metabolism proteins (GAA and GAPDH; Figure 3—source data 1) (Lachmandas et al., 2016; McCall et al., 2011).

Changes in transcription in monocytes of P.falciparum infected Fulani were associated with a differential regulation of innate immune response pathways, in particular, the activation of the inflammasome. Activation of the inflammasome occurs in two stages: first, a ‘priming’ signal activates expression of both inflammasome components and its target proteins; then, a second ‘activation’ signal promotes assembly of inflammasome components into an active complex that processes target proteins into their biologically active forms (He et al., 2016). Our results showed significantly increased expression of an inflammasome pathway activator (P2RX7) in uninfected Fulani compared to Mossi, and then significantly increased levels of target protein activation (IL-1β and IL-18) together with reduced expression of inflammasome pathway components in infected Fulani. This is consistent with reports that activation of the inflammasome results in downregulation of expression of its components. Collectively, this suggests that the Fulani have higher baseline levels of expression of inflammasome pathway components, resulting in stronger inflammasome activation following P.falciparum infection.

Recently, a small number of reports have begun to address the role of the inflammasome in the immune response in malaria. The available evidence indicates P.falciparum infection can drive inflammasome activation in human patients: In mice, hemozoin or symptomatic Plasmodium infection trigger inflammasome formation in erythrocytes and monocytes, respectively (Ataide et al., 2014; Kalantari et al., 2014); monocytes from P.vivax malaria patients contain inflammasome components (Ataide et al., 2014); P.falciparum and P.vivax DNA containing immunocomplexes induce inflammasome assembly and caspase-1 activation in human monocytes in culture (Hirako et al., 2015); and primed human monocyte-derived macrophages, incubated with antibody-opsonized P.falciparum infected erythrocytes, activate the inflammasome and secrete IL-1β (Zhou et al., 2012). Our results showing higher levels of inflammasome activation in P.falciparum infected Fulani support these findings, and further, suggest that activation of the inflammasome may be protective and involved in a more effective immune response in malaria.

In regions of hyperendemic malaria, such as where the Fulani and the Mossi included in this study reside, individuals commonly experience multiple P.falciparum infections in a transmission season. In the case of other infections, monocytes and other cells of the innate immune system have been reported to develop ‘memory’, enabling more efficient response to secondary infections (Netea et al., 2016). In contrast to innate immune tolerance, this response is typified by increased expression of different gene modules, upregulated proinflammatory cytokine response (Saeed et al., 2014), and a shift toward aerobic glycolysis (Cheng et al., 2014). This ‘trained immunity’ is based on epigenetic reprogramming of the innate immune cells (Netea et al., 2016; Glass and Natoli, 2016).

We hypothesised that the underlying mechanism for the stronger transcriptional response in monocytes from infected Fulani is caused by epigenetic and chromatin differences between Fulani and Mossi. However, the mechanisms mediating the observed transcriptional response in monocytes from infected Fulani were not correlated to changes in DNA methylation. Instead, our results lead us to propose that the transcriptional response in monocytes from infected Fulani is a result of an altered chromatin landscape caused by differential expression of chromatin remodelling and histone modification genes upon infection. Changes in chromatin structures and nuclear architecture, which depend on epigenetic changes as well as on density and spacing of nucleosomes, occur both during differentiation and activation of immune cells (Schultze, 2017; Netea et al., 2016; Glass and Natoli, 2016), and they drive changes in gene expression. The chromatin alterations predicted in Fulani are complex, since differentially expressed genes are classified both as activators and repressors; for example, histone modifying enzymes such as SUV39H1 and SUV420H1, which are responsible for establishing heterochromatin were downregulated, as were those involved in establishing euchromain and activate promoters, such as SET1 and SWI/SNF. In addition, non-coding RNAs contribute to the induction of chromatin states (Rutenberg-Schoenberg et al., 2016) and the few DE genes upregulated in the infected Fulani (144/1239) were enriched in non-coding RNA genes. Our conclusion that P.falciparum infections induce alteration in the chromatin landscape of monocytes is further supported by the observation that DE genes in Fulani monocytes often cluster in regions. Interestingly, one of these regions, 8q24.3 contains: the c-Myc gene; GSDMD, encoding inflammasome substrate gasdermin D (Liang and Liu, 2016); and a novel, uncharacterised locus of resistance to severe malaria (Malaria Genomic Epidemiology Network et al., 2015). Taken together we suggest that genome wide chromatin alterations occur as a result of P.falciparum infection in monocytes from Fulani, enabling a heightened transcriptional response.

Cells of the innate immune system, such as monocytes, macrophages and NK cells, have been shown to exhibit a memory alongside the more well studied memory of the adaptive immune system. The innate memory functions, such as ‘immune tolerance’ and ‘trained immunity’, can prepare the response to a second stimulation after an earlier first infection. Studies in model systems show that signalling pathways and transcription factors activated by the initial stimulus establish different histone modifications and nucleosome occupancy at specific sites (Foster et al., 2007; Netea et al., 2016; Glass and Natoli, 2016; Quintin et al., 2014; Hoeksema and de Winther, 2016). These imposed changes cause differences in the transcriptional response to subsequent infections. Trained immunity is characterised by an increased responsiveness of innate immune cells, typified by increased pro-inflammatory cytokine release and antimicrobial activity (Rizzetto et al., 2016; Netea and van der Meer, 2017) that can persit months after an initial stimulus (Netea et al., 2016; Quintin et al., 2014). Trained immunity correlates with epigenetic reprogramming at certain sites; ChIP sequencing analysis of monocytes show higher levels of H3K4me1/2 and H3K27Ac at specific gene promoters and enhancers, many of which are involved in pro-inflammatory response, metabolism, and phagocytosis (Saeed et al., 2014; Cheng et al., 2014; Novakovic et al., 2016). Our results show a response that resembles trained immunity in the Fulani. For example, chromatin factors that are involved in H3K4-methylation were significantly differentially expressed. Further, differentially expressed genes reflect typical processes associated with trained immunity, including altered glucose metabolism, lysosome function, and a pro-inflammatory state. We were also able to validate that uninfected Fulani have higher levels of pro-inflammatory cytokines. However, it is difficult to directly compare published data describing the initial and subsequent responses in models of controlled infection, to the responses we observed here in members of a natural population that undergo multiple infections during a malaria transmission season. We do not know when the changes underlying the transcriptional response are established in Fulani individuals – during a recent infection, early in the transmission season, or even earlier in life, during immune development. Nevertheless, our results suggest that in monocytes of uninfected Fulani, chromatin is already set in ‘primed’ state, driving the observed heightened transcriptional response and pro-inflammatory state. Thus, Fulani display a ‘high alert’ immune state, enabling a stronger reaction upon P.falciparum infection.

1. 1. Jaclyn E Quin
   2. Ioana Bujila
   3. Ying Qu
   4. Andreas Lennartsson
   5. Ann-Kristin Östlund Farrants

   (2017) Major transcriptional changes observed in the Fulani; an ethnic group less susceptible to malaria

   Publicly available at the NCBI Gene Expression Omnibus (accession no. GSE100563).

   https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100563

1. 1. Allison AC

   (2009) Genetic control of resistance to human malaria

   Current Opinion in Immunology 21:499–505.

   https://doi.org/10.1016/j.coi.2009.04.001

   • PubMed
   • Google Scholar
2. 1. Arama C
   2. Giusti P
   3. Boström S
   4. Dara V
   5. Traore B
   6. Dolo A
   7. Doumbo O
   8. Varani S
   9. Troye-Blomberg M

   (2011) Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria

   PLoS One 6:e18319.

   https://doi.org/10.1371/journal.pone.0018319

   • PubMed
   • Google Scholar
3. 1. Arama C
   2. Maiga B
   3. Dolo A
   4. Kouriba B
   5. Traoré B
   6. Crompton PD
   7. Pierce SK
   8. Troye-Blomberg M
   9. Miller LH
   10. Doumbo OK

   (2015a) Ethnic differences in susceptibility to malaria: what have we learned from immuno-epidemiological studies in West Africa?

   Acta Tropica 146:152–156.

   https://doi.org/10.1016/j.actatropica.2015.03.023

   • PubMed
   • Google Scholar
4. 1. Arama C
   2. Skinner J
   3. Doumtabe D
   4. Portugal S
   5. Tran TM
   6. Jain A
   7. Traore B
   8. Doumbo OK
   9. Davies DH
   10. Troye-Blomberg M
   11. Dolo A
   12. Felgner PL
   13. Crompton PD

   (2015b) Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens

   Open Forum Infectious Diseases 2:ofv118.

   https://doi.org/10.1093/ofid/ofv118

   • PubMed
   • Google Scholar
5. 1. Ataide MA
   2. Andrade WA
   3. Zamboni DS
   4. Wang D
   5. Souza MC
   6. Franklin BS
   7. Elian S
   8. Martins FS
   9. Pereira D
   10. Reed G
   11. Fitzgerald KA
   12. Golenbock DT
   13. Gazzinelli RT

   (2014) Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection

   PLoS Pathogens 10:e1003885.

   https://doi.org/10.1371/journal.ppat.1003885

   • PubMed
   • Google Scholar
6. 1. Bolad A
   2. Farouk SE
   3. Israelsson E
   4. Dolo A
   5. Doumbo OK
   6. Nebié I
   7. Maiga B
   8. Kouriba B
   9. Luoni G
   10. Sirima BS
   11. Modiano D
   12. Berzins K
   13. Troye-Blomberg M

   (2005) Distinct interethnic differences in immunoglobulin G class/subclass and immunoglobulin M antibody responses to malaria antigens but not in immunoglobulin G responses to nonmalarial antigens in sympatric tribes living in West Africa

   Scandinavian Journal of Immunology 61:380–386.

   https://doi.org/10.1111/j.1365-3083.2005.01587.x

   • PubMed
   • Google Scholar
7. 1. Boraschi D
   2. Tagliabue A

   (2013) The interleukin-1 receptor family

   Seminars in Immunology 25:394–407.

   https://doi.org/10.1016/j.smim.2013.10.023

   • PubMed
   • Google Scholar
8. 1. Boström S
   2. Giusti P
   3. Arama C
   4. Persson JO
   5. Dara V
   6. Traore B
   7. Dolo A
   8. Doumbo O
   9. Troye-Blomberg M

   (2012) Changes in the levels of cytokines, chemokines and malaria-specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali

   Malaria Journal 11:109.

   https://doi.org/10.1186/1475-2875-11-109

   • PubMed
   • Google Scholar
9. 1. Cheng SC
   2. Quintin J
   3. Cramer RA
   4. Shepardson KM
   5. Saeed S
   6. Kumar V
   7. Giamarellos-Bourboulis EJ
   8. Martens JH
   9. Rao NA
   10. Aghajanirefah A
   11. Manjeri GR
   12. Li Y
   13. Ifrim DC
   14. Arts RJ
   15. van der Veer BM
   16. van der Meer BM
   17. Deen PM
   18. Logie C
   19. O'Neill LA
   20. Willems P
   21. van de Veerdonk FL
   22. van der Meer JW
   23. Ng A
   24. Joosten LA
   25. Wijmenga C
   26. Stunnenberg HG
   27. Xavier RJ
   28. Netea MG

   (2014) mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity

   Science 345:1250684.

   https://doi.org/10.1126/science.1250684

   • PubMed
   • Google Scholar
10. 1. Cherif M
    2. Amoako-Sakyi D
    3. Dolo A
    4. Pearson JO
    5. Gyan B
    6. Obiri-Yeboah D
    7. Nebie I
    8. Sirima SB
    9. Doumbo O
    10. Troye-Blomberg M
    11. Bakary M

    (2016) Distribution of FcγR gene polymorphisms among two sympatric populations in Mali: differing allele frequencies, associations with malariometric indices and implications for genetic susceptibility to malaria

    Malaria Journal 15:29.

    https://doi.org/10.1186/s12936-015-1082-8

    • PubMed
    • Google Scholar
11. 1. Cherif MK
    2. Sanou GS
    3. Bougouma EC
    4. Diarra A
    5. Ouédraogo A
    6. Dolo A
    7. Troye-Blomberg M
    8. Cavanagh DR
    9. Theisen M
    10. Modiano D
    11. Sirima SB
    12. Nebié I

    (2015) Is Fc gamma receptor IIA (FcγRIIA) polymorphism associated with clinical malaria and Plasmodium falciparum specific antibody levels in children from Burkina Faso?

    Acta Tropica 142:41–46.

    https://doi.org/10.1016/j.actatropica.2014.09.019

    • PubMed
    • Google Scholar
12. 1. Cherif MK
    2. Sanou GS
    3. Maiga B
    4. Israelsson E
    5. Ouédraogo AL
    6. Bougouma EC
    7. Diarra A
    8. Ouédraogo A
    9. Ouattara AS
    10. Troye-Blomberg M
    11. Dolo A
    12. Cavanagh DR
    13. Theisen M
    14. Modiano D
    15. Sirima SB
    16. Nebié I

    (2012) FcγRIIa polymorphism and anti-malaria-specific IgG and IgG subclass responses in populations differing in susceptibility to malaria in Burkina Faso

    Scandinavian Journal of Immunology 75:606–613.

    https://doi.org/10.1111/j.1365-3083.2012.02690.x

    • PubMed
    • Google Scholar
13. 1. Davis BK
    2. Roberts RA
    3. Huang MT
    4. Willingham SB
    5. Conti BJ
    6. Brickey WJ
    7. Barker BR
    8. Kwan M
    9. Taxman DJ
    10. Accavitti-Loper MA
    11. Duncan JA
    12. Ting JP

    (2011) Cutting edge: NLRC5-dependent activation of the inflammasome

    The Journal of Immunology 186:1333–1337.

    https://doi.org/10.4049/jimmunol.1003111

    • PubMed
    • Google Scholar
14. 1. Dev A
    2. Iyer S
    3. Razani B
    4. Cheng G

    (2011) NF-κB and innate immunity

    Current Topics in Microbiology and Immunology 349:115–143.

    https://doi.org/10.1007/82_2010_102

    • PubMed
    • Google Scholar
15. 1. Esposito F
    2. Lombardi S
    3. Modiano D
    4. Zavala F
    5. Reeme J
    6. Lamizana L
    7. Coluzzi M
    8. Nussenzweig RS

    (1988) Prevalence and levels of antibodies to the circumsporozoite protein of Plasmodium falciparum in an endemic area and their relationship to resistance against malaria infection

    Transactions of the Royal Society of Tropical Medicine and Hygiene 82:827–832.

    https://doi.org/10.1016/0035-9203(88)90007-7

    • PubMed
    • Google Scholar
16. 1. Farouk SE
    2. Dolo A
    3. Bereczky S
    4. Kouriba B
    5. Maiga B
    6. Färnert A
    7. Perlmann H
    8. Hayano M
    9. Montgomery SM
    10. Doumbo OK
    11. Troye-Blomberg M

    (2005) Different antibody- and cytokine-mediated responses to Plasmodium falciparum parasite in two sympatric ethnic tribes living in Mali

    Microbes and Infection 7:110–117.

    https://doi.org/10.1016/j.micinf.2004.09.012

    • PubMed
    • Google Scholar
17. 1. Foster SL
    2. Hargreaves DC
    3. Medzhitov R

    (2007) Gene-specific control of inflammation by TLR-induced chromatin modifications

    Nature 447:972–978.

    https://doi.org/10.1038/nature05836

    • PubMed
    • Google Scholar
18. 1. Galli GG
    2. Carrara M
    3. Francavilla C
    4. de Lichtenberg KH
    5. Olsen JV
    6. Calogero RA
    7. Lund AH

    (2013) Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells

    Molecular and Cellular Biology 33:4504–4516.

    https://doi.org/10.1128/MCB.00545-13

    • PubMed
    • Google Scholar
19. 1. Glass CK
    2. Natoli G

    (2016) Molecular control of activation and priming in macrophages

    Nature Immunology 17:26–33.

    https://doi.org/10.1038/ni.3306

    • PubMed
    • Google Scholar
20. 1. Guo H
    2. Callaway JB
    3. Ting JP

    (2015) Inflammasomes: mechanism of action, role in disease, and therapeutics

    Nature Medicine 21:677–687.

    https://doi.org/10.1038/nm.3893

    • PubMed
    • Google Scholar
21. 1. He Y
    2. Hara H
    3. Núñez G

    (2016) Mechanism and Regulation of NLRP3 Inflammasome Activation

    Trends in Biochemical Sciences 41:1012–1021.

    https://doi.org/10.1016/j.tibs.2016.09.002

    • PubMed
    • Google Scholar
22. 1. Hirako IC
    2. Gallego-Marin C
    3. Ataide MA
    4. Andrade WA
    5. Gravina H
    6. Rocha BC
    7. de Oliveira RB
    8. Pereira DB
    9. Vinetz J
    10. Diamond B
    11. Ram S
    12. Golenbock DT
    13. Gazzinelli RT

    (2015) DNA-Containing Immunocomplexes Promote Inflammasome Assembly and Release of Pyrogenic Cytokines by CD14+ CD16+ CD64high CD32low Inflammatory Monocytes from Malaria Patients

    mBio 6:e01605-15–01615.

    https://doi.org/10.1128/mBio.01605-15

    • PubMed
    • Google Scholar
23. 1. Hoeksema MA
    2. de Winther MP

    (2016) Epigenetic Regulation of Monocyte and Macrophage Function

    Antioxidants & Redox Signaling 25:758–774.

    https://doi.org/10.1089/ars.2016.6695

    • PubMed
    • Google Scholar
24. 1. Kalantari P
    2. DeOliveira RB
    3. Chan J
    4. Corbett Y
    5. Rathinam V
    6. Stutz A
    7. Latz E
    8. Gazzinelli RT
    9. Golenbock DT
    10. Fitzgerald KA

    (2014) Dual engagement of the NLRP3 and AIM2 inflammasomes by plasmodium-derived hemozoin and DNA during malaria

    Cell Reports 6:196–210.

    https://doi.org/10.1016/j.celrep.2013.12.014

    • PubMed
    • Google Scholar
25. 1. Kobayashi E
    2. Suzuki T
    3. Yamamoto M

    (2013) Roles nrf2 plays in myeloid cells and related disorders

    Oxidative Medicine and Cellular Longevity 2013:529219.

    https://doi.org/10.1155/2013/529219

    • PubMed
    • Google Scholar
26. 1. Lachmandas E
    2. Beigier-Bompadre M
    3. Cheng SC
    4. Kumar V
    5. van Laarhoven A
    6. Wang X
    7. Ammerdorffer A
    8. Boutens L
    9. de Jong D
    10. Kanneganti TD
    11. Gresnigt MS
    12. Ottenhoff TH
    13. Joosten LA
    14. Stienstra R
    15. Wijmenga C
    16. Kaufmann SH
    17. van Crevel R
    18. Netea MG

    (2016) Rewiring cellular metabolism via the AKT/mTOR pathway contributes to host defence against Mycobacterium tuberculosis in human and murine cells

    European Journal of Immunology 46:2574–2586.

    https://doi.org/10.1002/eji.201546259

    • PubMed
    • Google Scholar
27. 1. Liang H
    2. Liu Y

    (2016) Gasdermins pore cell membrane to pyroptosis

    Science China Life Sciences 59:1090–1092.

    https://doi.org/10.1007/s11427-016-0243-4

    • PubMed
    • Google Scholar
28. 1. Lulli P
    2. Mangano VD
    3. Onori A
    4. Batini C
    5. Luoni G
    6. Sirima BS
    7. Nebie I
    8. Chessa L
    9. Petrarca V
    10. Modiano D

    (2009) HLA-DRB1 and -DQB1 loci in three west African ethnic groups: genetic relationship with sub-Saharan African and European populations

    Human Immunology 70:903–909.

    https://doi.org/10.1016/j.humimm.2009.07.025

    • PubMed
    • Google Scholar
29. 1. Maiga B
    2. Dolo A
    3. Touré O
    4. Dara V
    5. Tapily A
    6. Campino S
    7. Sepulveda N
    8. Corran P
    9. Rockett K
    10. Clark TG
    11. Blomberg MT
    12. Doumbo OK

    (2014) Fc gamma receptor IIa-H131R polymorphism and malaria susceptibility in sympatric ethnic groups, Fulani and Dogon of Mali

    Scandinavian Journal of Immunology 79:43–50.

    https://doi.org/10.1111/sji.12122

    • PubMed
    • Google Scholar
30. 1. Malaria Genomic Epidemiology Network
    2. Band G
    3. Rockett KA
    4. Spencer CC
    5. Kwiatkowski DP

    (2015) A novel locus of resistance to severe malaria in a region of ancient balancing selection

    Nature 526:253–257.

    https://doi.org/10.1038/nature15390

    • PubMed
    • Google Scholar
31. 1. Mangano VD
    2. Kabore Y
    3. Bougouma EC
    4. Verra F
    5. Sepulveda N
    6. Bisseye C
    7. Santolamazza F
    8. Avellino P
    9. Tiono AB
    10. Diarra A
    11. Nebie I
    12. Rockett KA
    13. Sirima SB
    14. Modiano D
    15. MalariaGEN Consortium

    (2015) Novel Insights Into the Protective Role of Hemoglobin S and C Against Plasmodium falciparum Parasitemia

    Journal of Infectious Diseases 212:626–634.

    https://doi.org/10.1093/infdis/jiv098

    • PubMed
    • Google Scholar
32. 1. Martens JH
    2. Mandoli A
    3. Simmer F
    4. Wierenga BJ
    5. Saeed S
    6. Singh AA
    7. Altucci L
    8. Vellenga E
    9. Stunnenberg HG

    (2012) ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia

    Blood 120:4038–4048.

    https://doi.org/10.1182/blood-2012-05-429050

    • PubMed
    • Google Scholar
33. 1. McCall CE
    2. El Gazzar M
    3. Liu T
    4. Vachharajani V
    5. Yoza B

    (2011) Epigenetics, bioenergetics, and microRNA coordinate gene-specific reprogramming during acute systemic inflammation

    Journal of Leukocyte Biology 90:439–446.

    https://doi.org/10.1189/jlb.0211075

    • PubMed
    • Google Scholar
34. 1. McCall MB
    2. Hopman J
    3. Daou M
    4. Maiga B
    5. Dara V
    6. Ploemen I
    7. Nganou-Makamdop K
    8. Niangaly A
    9. Tolo Y
    10. Arama C
    11. Bousema JT
    12. van der Meer JW
    13. van der Ven AJ
    14. Troye-Blomberg M
    15. Dolo A
    16. Doumbo OK
    17. Sauerwein RW

    (2010) Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali

    The Journal of Infectious Diseases 201:142–152.

    https://doi.org/10.1086/648596

    • PubMed
    • Google Scholar
35. 1. Modiano D
    2. Luoni G
    3. Sirima BS
    4. Lanfrancotti A
    5. Petrarca V
    6. Cruciani F
    7. Simporé J
    8. Ciminelli BM
    9. Foglietta E
    10. Grisanti P
    11. Bianco I
    12. Modiano G
    13. Coluzzi M

    (2001) The lower susceptibility to Plasmodium falciparum malaria of Fulani of Burkina Faso (west Africa) is associated with low frequencies of classic malaria-resistance genes

    Transactions of the Royal Society of Tropical Medicine and Hygiene 95:149-+.

    https://doi.org/10.1016/S0035-9203(01)90141-5

    • PubMed
    • Google Scholar
36. 1. Modiano D
    2. Petrarca V
    3. Sirima BS
    4. Nebié I
    5. Diallo D
    6. Esposito F
    7. Coluzzi M

    (1996) Different response to Plasmodium falciparum malaria in west African sympatric ethnic groups

    PNAS 93:13206–13211.

    https://doi.org/10.1073/pnas.93.23.13206

    • PubMed
    • Google Scholar
37. 1. Netea MG
    2. Joosten LA
    3. Latz E
    4. Mills KH
    5. Natoli G
    6. Stunnenberg HG
    7. O'Neill LA
    8. Xavier RJ
    9. L. A. O'Neill, R. J

    (2016) Trained immunity: A program of innate immune memory in health and disease

    Science 352:aaf1098.

    https://doi.org/10.1126/science.aaf1098

    • PubMed
    • Google Scholar
38. 1. Netea MG
    2. van der Meer JW

    (2017) Trained Immunity: An Ancient Way of Remembering

    Cell Host & Microbe 21:297–300.

    https://doi.org/10.1016/j.chom.2017.02.003

    • PubMed
    • Google Scholar
39. 1. Novakovic B
    2. Habibi E
    3. Wang SY
    4. Arts RJ
    5. Davar R
    6. Megchelenbrink W
    7. Kim B
    8. Kuznetsova T
    9. Kox M
    10. Zwaag J
    11. Matarese F
    12. van Heeringen SJ
    13. Janssen-Megens EM
    14. Sharifi N
    15. Wang C
    16. Keramati F
    17. Schoonenberg V
    18. Flicek P
    19. Clarke L
    20. Pickkers P
    21. Heath S
    22. Gut I
    23. Netea MG
    24. Martens JH
    25. Logie C
    26. Stunnenberg HG

    (2016) β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance

    Cell 167:e1314.

    https://doi.org/10.1016/j.cell.2016.09.034

    • PubMed
    • Google Scholar
40. 1. Perdijk O
    2. Arama C
    3. Giusti P
    4. Maiga B
    5. Troye-Blomberg M
    6. Dolo A
    7. Doumbo O
    8. Persson JO
    9. Boström S

    (2013) Haptoglobin phenotype prevalence and cytokine profiles during Plasmodium falciparum infection in Dogon and Fulani ethnic groups living in Mali

    Malaria Journal 12:432.

    https://doi.org/10.1186/1475-2875-12-432

    • PubMed
    • Google Scholar
41. 1. Petrarca V
    2. Petrangeli G
    3. Rossi P
    4. Sabatinelli G

    (1986)

    [Chromosomal study of Anopheles gambiae and Anopheles arabiensis in Ouagadougou (Burkina Faso) and various neighboring villages]

    Parassitologia 28:41–61.

    • PubMed
    • Google Scholar
42. 1. Portugal S
    2. Doumtabe D
    3. Traore B
    4. Miller LH
    5. Troye-Blomberg M
    6. Doumbo OK
    7. Dolo A
    8. Pierce SK
    9. Crompton PD

    (2012) B cell analysis of ethnic groups in Mali with differential susceptibility to malaria

    Malaria Journal 11:162.

    https://doi.org/10.1186/1475-2875-11-162

    • PubMed
    • Google Scholar
43. 1. Quintin J
    2. Cheng SC
    3. van der Meer JW
    4. Netea MG

    (2014) Innate immune memory: towards a better understanding of host defense mechanisms

    Current Opinion in Immunology 29:1–7.

    https://doi.org/10.1016/j.coi.2014.02.006

    • PubMed
    • Google Scholar
44. 1. Riddell J
    2. Gazit R
    3. Garrison BS
    4. Guo G
    5. Saadatpour A
    6. Mandal PK
    7. Ebina W
    8. Volchkov P
    9. Yuan GC
    10. Orkin SH
    11. Rossi DJ

    (2014) Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors

    Cell 157:549–564.

    https://doi.org/10.1016/j.cell.2014.04.006

    • PubMed
    • Google Scholar
45. 1. Rizzetto L
    2. Ifrim DC
    3. Moretti S
    4. Tocci N
    5. Cheng SC
    6. Quintin J
    7. Renga G
    8. Oikonomou V
    9. De Filippo C
    10. Weil T
    11. Blok BA
    12. Lenucci MS
    13. Santos MA
    14. Romani L
    15. Netea MG
    16. Cavalieri D

    (2016) Fungal Chitin Induces Trained Immunity in Human Monocytes during Cross-talk of the Host with Saccharomyces cerevisiae

    Journal of Biological Chemistry 291:7961–7972.

    https://doi.org/10.1074/jbc.M115.699645

    • PubMed
    • Google Scholar
46. 1. Rizzo C
    2. Ronca R
    3. Fiorentino G
    4. Verra F
    5. Mangano V
    6. Poinsignon A
    7. Sirima SB
    8. Nèbiè I
    9. Lombardo F
    10. Remoue F
    11. Coluzzi M
    12. Petrarca V
    13. Modiano D
    14. Arcà B

    (2011) Humoral response to the Anopheles gambiae salivary protein gSG6: a serological indicator of exposure to Afrotropical malaria vectors

    PLoS One 6:e17980.

    https://doi.org/10.1371/journal.pone.0017980

    • PubMed
    • Google Scholar
47. 1. Rutenberg-Schoenberg M
    2. Sexton AN
    3. Simon MD

    (2016) The Properties of Long Noncoding RNAs That Regulate Chromatin

    Annual Review of Genomics and Human Genetics 17:69–94.

    https://doi.org/10.1146/annurev-genom-090314-024939

    • PubMed
    • Google Scholar
48. 1. Saeed S
    2. Logie C
    3. Francoijs KJ
    4. Frigè G
    5. Romanenghi M
    6. Nielsen FG
    7. Raats L
    8. Shahhoseini M
    9. Huynen M
    10. Altucci L
    11. Minucci S
    12. Martens JH
    13. Stunnenberg HG

    (2012) Chromatin accessibility, p300, and histone acetylation define PML-RARα and AML1-ETO binding sites in acute myeloid leukemia

    Blood 120:3058–3068.

    https://doi.org/10.1182/blood-2011-10-386086

    • PubMed
    • Google Scholar
49. 1. Saeed S
    2. Quintin J
    3. Kerstens HH
    4. Rao NA
    5. Aghajanirefah A
    6. Matarese F
    7. Cheng SC
    8. Ratter J
    9. Berentsen K
    10. van der Ent MA
    11. Sharifi N
    12. Janssen-Megens EM
    13. Ter Huurne M
    14. Mandoli A
    15. van Schaik T
    16. Ng A
    17. Burden F
    18. Downes K
    19. Frontini M
    20. Kumar V
    21. Giamarellos-Bourboulis EJ
    22. Ouwehand WH
    23. van der Meer JW
    24. Joosten LA
    25. Wijmenga C
    26. Martens JH
    27. Xavier RJ
    28. Logie C
    29. Netea MG
    30. Stunnenberg HG

    (2014) Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity

    Science 345:1251086.

    https://doi.org/10.1126/science.1251086

    • PubMed
    • Google Scholar
50. 1. Schultze JL

    (2017) Chromatin Remodeling in Monocyte and Macrophage Activation

    Advances in Protein Chemistry and Structural Biology 106:1–15.

    https://doi.org/10.1016/bs.apcsb.2016.09.001

    • PubMed
    • Google Scholar
51. 1. Sharma D
    2. Kanneganti TD

    (2016) The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation

    The Journal of Cell Biology 213:617–629.

    https://doi.org/10.1083/jcb.201602089

    • PubMed
    • Google Scholar
52. 1. Shokoples SE
    2. Ndao M
    3. Kowalewska-Grochowska K
    4. Yanow SK

    (2009) Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections

    Journal of Clinical Microbiology 47:975–980.

    https://doi.org/10.1128/JCM.01858-08

    • PubMed
    • Google Scholar
53. 1. Torcia MG
    2. Santarlasci V
    3. Cosmi L
    4. Clemente A
    5. Maggi L
    6. Mangano VD
    7. Verra F
    8. Bancone G
    9. Nebie I
    10. Sirima BS
    11. Liotta F
    12. Frosali F
    13. Angeli R
    14. Severini C
    15. Sannella AR
    16. Bonini P
    17. Lucibello M
    18. Maggi E
    19. Garaci E
    20. Coluzzi M
    21. Cozzolino F
    22. Annunziato F
    23. Romagnani S
    24. Modiano D

    (2008) Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria

    PNAS 105:646–651.

    https://doi.org/10.1073/pnas.0709969105

    • PubMed
    • Google Scholar
54. 1. Vafa M
    2. Israelsson E
    3. Maiga B
    4. Dolo A
    5. Doumbo OK
    6. Troye-Blomberg M

    (2009) Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali

    Acta Tropica 109:12–16.

    https://doi.org/10.1016/j.actatropica.2008.09.001

    • PubMed
    • Google Scholar
55. 1. Wiley JS
    2. Sluyter R
    3. Gu BJ
    4. Stokes L
    5. Fuller SJ

    (2011) The human P2X7 receptor and its role in innate immunity

    Tissue Antigens 78:321–332.

    https://doi.org/10.1111/j.1399-0039.2011.01780.x

    • PubMed
    • Google Scholar
56. 1. Yang W
    2. Ernst P

    (2017) SET/MLL family proteins in hematopoiesis and leukemia

    International Journal of Hematology 105:7–16.

    https://doi.org/10.1007/s12185-016-2118-8

    • PubMed
    • Google Scholar
57. 1. Yordy JS
    2. Muise-Helmericks RC

    (2000) Signal transduction and the Ets family of transcription factors

    Oncogene 19:6503–6513.

    https://doi.org/10.1038/sj.onc.1204036

    • PubMed
    • Google Scholar
58. 1. Zhou J
    2. Ludlow LE
    3. Hasang W
    4. Rogerson SJ
    5. Jaworowski A

    (2012) Opsonization of malaria-infected erythrocytes activates the inflammasome and enhances inflammatory cytokine secretion by human macrophages

    Malaria Journal 11:343.

    https://doi.org/10.1186/1475-2875-11-343

    • PubMed
    • Google Scholar

Author details

1. Jaclyn E Quin

   Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden

   Contribution

   Conceptualization, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing—original draft, Writing—review and editing

   Contributed equally with

   Ioana Bujila, Mariama Chérif and Guillaume S Sanou

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-7757-7295

2. Ioana Bujila

   Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden

   Contribution

   Conceptualization, Formal analysis, Investigation, Methodology, Writing—review and editing

   Contributed equally with

   Jaclyn E Quin, Mariama Chérif and Guillaume S Sanou

   Competing interests

   No competing interests declared

3. Mariama Chérif

   1. Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso
   2. Université Polytechnique de Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso

   Contribution

   Conceptualization, Validation, Investigation, Methodology, Writing—review and editing

   Contributed equally with

   Jaclyn E Quin, Ioana Bujila and Guillaume S Sanou

   Competing interests

   No competing interests declared

4. Guillaume S Sanou

   Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso

   Contribution

   Investigation, Project administration, Writing—review and editing

   Contributed equally with

   Jaclyn E Quin, Ioana Bujila and Mariama Chérif

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-0536-616X

5. Ying Qu

   Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden

   Contribution

   Formal analysis, Visualization, Writing—review and editing

   Competing interests

   No competing interests declared

6. Manijeh Vafa Homann

   Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Stockholm, Sweden

   Contribution

   Investigation, Methodology, Writing—review and editing

   Competing interests

   No competing interests declared

7. Anna Rolicka

   Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden

   Present address

   Faculty of Animal Sciences Department of Genetics and Animal Breeding, SGGW, Warsaw University of Life Sciences, Warszawa, Poland

   Contribution

   Investigation, Writing—review and editing

   Competing interests

   No competing interests declared

8. Sodiomon B Sirima

   Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso

   Contribution

   Project administration, As director of Centre National de Recherche et de Formation sur le Paludisme, he was instrumental in the co-ordination of ethical compliance and material aquisition in Burkina Faso. Without his support, the study could not have been conducted

   Competing interests

   No competing interests declared

9. Mary A O'Connell

   Central European Institute of Technology, Brno, Czech Republic

   Contribution

   Conceptualization, Investigation, Methodology, Writing—review and editing

   Competing interests

   No competing interests declared

10. Andreas Lennartsson

    Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden

    Contribution

    Conceptualization, Formal analysis, Investigation, Methodology, Writing—review and editing

    Competing interests

    No competing interests declared

11. Marita Troye-Blomberg

    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden

    Contribution

    Conceptualization, Investigation, Methodology, Writing—review and editing

    Competing interests

    No competing interests declared

12. Issa Nebie

    Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso

    Contribution

    Conceptualization, Investigation, Project administration, Writing—review and editing

    Competing interests

    No competing interests declared

13. Ann-Kristin Östlund Farrants

    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden

    Contribution

    Conceptualization, Formal analysis, Supervision, Funding acquisition, Investigation, Methodology, Writing—original draft, Writing—review and editing

    For correspondence

    anki.ostlund@su.se

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0001-9225-3264

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