Early Mucosal Sensing of SIV Infection by Paneth Cells Induces IL-1β Production and Initiates Gut Epithelial Disruption

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The loss of intestinal CD4+ T cells in chronic HIV infection is associated with impaired immune responses to pathogens, aberrant immune activation, and defects in the gut epithelial barrier. While much is known about the pathogenesis of HIV in chronic disease, less is known about the defects that occur prior to gut CD4+ T cell depletion and whether these defects alter host interactions with pathogenic and commensal bacteria. Using a non-human primate model of HIV infection, we examined the immune and structural changes in the gastrointestinal tract 2.5 days following SIV infection. Paneth cells, in immediate proximity of SIV infected immune cells, generated a robust IL-1β response. This IL-1β response correlated with defects in epithelial tight junctions and preceded the IFN-α response, which is characteristic of innate antiviral immune responses. Despite this inflammatory environment, we did not observe defects in mucosal immune responses to pathogenic or commensal bacteria. In fact, commensal bacteria were able to dampen the IL-1β response and ameliorate tight junction defects. Our study highlights the importance of the gut epithelium in HIV infection, not just as a target of pathogenesis but also the initiator of immune responses to viral infection, which can be strongly influenced by commensal bacteria.

Vyšlo v časopise: Early Mucosal Sensing of SIV Infection by Paneth Cells Induces IL-1β Production and Initiates Gut Epithelial Disruption. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004311
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004311

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