IL22 and CD160 play additive roles in the mucosal host response to Clostridium difficult infection in mice (INM8P.435)

Abstract

Abstract We have previously shown the significant up-regulation of Il22 and increased phosphorylation of STAT3 as part of the mucosal response to C. difficile VPI 10463 infection. Others have shown that phosphorylation of STAT3 at mucosal surfaces includes IL22- and CD160-mediated components. The current study sought to determine the potential role(s) of IL22 and/or CD160 in the mucosal response to C. difficile infection. Infection of mice with C. difficile 630 led to the significant induction of STAT3 phosphorylation and a very similar set of genes in the colon as we had reported previously. C. difficile-infected mice treated with anti-IL22, anti-CD160 or both showed significantly reduced STAT3 phosphorylation in comparison to C. difficile-infected mice that had received neither antibody. In addition, C. difficile-infected mice treated with anti-IL22/CD160 induced a smaller set of genes, and at significantly lower levels than the untreated C. difficile-infected mice. These included pro-inflammatory chemokines and cytokines and anti-bacterial peptides. In addition, mice treated with anti-IL22/CD160 had a lower influx of neutrophils than the other 3 infected groups. These data demonstrate that IL22 and CD160 are together responsible for a significant fraction of the colonic STAT3 phosphorylation in C. difficile infection. They also underscore the additive effects of IL22 and CD160 in mediating both the pro-inflammatory and pro-survival aspects of the mucosal response in this infection.