A Novel Mouse Model of Gastroenteritis Reveals Key Pro-inflammatory and Tissue Protective Roles for Toll-like Receptor Signaling during Infection

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Research into the key virulence strategies of the bacterial pathogen Campylobacter jejuni, as well as the host immune responses that develop against this microbe have, in many ways, been limited by the lack of relevant animal models. Here we describe the use of Sigirr deficient (−/−) mice as a model for C. jejuni pathogenesis. Not only do Sigirr−/− mice develop significant intestinal inflammation in response to colonization by C. jejuni, but the ability of this pathogen to trigger gastroenteritis was dependent on key virulence factors. We also found that the induction of the inflammatory and Th1/Th17 immune responses to infection in these mice depended on specific Toll-like receptors, principally TLR4, which we identified as the main driver of inflammation. In contrast, TLR2 signaling was found to protect mucosal integrity, with Tlr2−/−/Sigirr−/− mice suffering exaggerated mucosal damage and inflammation. Notably, we found that C. jejuni's capsule helped conceal it from the host's immune system as its loss led to significantly increased activation of host TLRs and exaggerated gastroenteritis. Our research shows that the increased sensitivity of Sigirr−/− mice can be used to generate a unique and exciting model that facilitates the study of C. jejuni pathogenesis as well as host immunity to this enteric pathogen.

Vyšlo v časopise: A Novel Mouse Model of Gastroenteritis Reveals Key Pro-inflammatory and Tissue Protective Roles for Toll-like Receptor Signaling during Infection. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004264
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004264

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