IL17 factors are early regulators in the gut epithelium during inflammatory response to Vibrio in the sea urchin larva
- The George Washington University, United States
- Sunnybrook Research Institute, Canada
- Saitama University, Japan
- University of Toronto, Canada
Abstract
IL17 cytokines are central mediators of mammalian immunity. In vertebrates, these factors derive from diverse cellular sources. Sea urchins share a molecular heritage with chordates that includes the IL17 system. Here, we characterize the role of epithelial expression of IL17 in the larval gut-associated immune response. The purple sea urchin genome encodes ten IL17 subfamilies (35 genes) and two IL17 receptors. Most of these subfamilies are conserved throughout echinoderms. Two IL17 subfamilies are sequentially strongly upregulated and attenuated in the gut epithelium in response to bacterial disturbance. IL17R1 signal perturbation results in reduced expression of several response genes including an IL17 subtype, indicating a potential feedback. A third IL17 subfamily is activated in adult immune cells indicating that expression in immune cells and epithelia is divided among families. The larva provides a tractable model to investigate the regulation and consequences of gut epithelial IL17 expression across the organism.
Data availability
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Strongylocentrotus purpuratus developmental transcriptomesPublicly available at the NCBI Gene Expression Omnibus (accession no: PRJNA81157).
Article and author information
Author details
Katherine M Buckley
Jonathan Patrick Rast
Funding
Canadian Institutes of Health Research (MOP74667)
- Jonathan Patrick Rast
Natural Sciences and Engineering Research Council of Canada (312221)
- Jonathan Patrick Rast
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal care and use protocols were approved by the Sunnybrook Research Institute Animal Care Committee
Copyright
© 2017, Buckley et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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IL17 factors are early regulators in the gut epithelium during inflammatory response to Vibrio in the sea urchin larva
eLife 6:e23481.
https://doi.org/10.7554/eLife.23481
Further reading
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The sea urchin may be a good model for understanding how immune responses work in humans and other vertebrates.
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- Immunology and Inflammation
- Microbiology and Infectious Disease
Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related deaths are a result of dysregulated inflammatory immune responses indicating the need to develop strategies to target inflammation. An important mediator of inflammation is extracellular adenosine triphosphate (ATP) that is released by inflamed host cells and tissues, and also by bacteria in a strain-specific and growth-dependent manner. Here, we investigated the mechanisms by which bacteria release ATP. Using genetic mutant strains of Escherichia coli (E. coli), we demonstrate that ATP release is dependent on ATP synthase within the inner bacterial membrane. In addition, impaired integrity of the outer bacterial membrane notably contributes to ATP release and is associated with bacterial death. In a mouse model of abdominal sepsis, local effects of bacterial ATP were analyzed using a transformed E. coli bearing an arabinose-inducible periplasmic apyrase hydrolyzing ATP to be released. Abrogating bacterial ATP release shows that bacterial ATP suppresses local immune responses, resulting in reduced neutrophil counts and impaired survival. In addition, bacterial ATP has systemic effects via its transport in outer membrane vesicles (OMV). ATP-loaded OMV are quickly distributed throughout the body and upregulated expression of genes activating degranulation in neutrophils, potentially contributing to the exacerbation of sepsis severity. This study reveals mechanisms of bacterial ATP release and its local and systemic roles in sepsis pathogenesis.
