Interleukin‐22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice

Summary Our previous work has shown the significant up‐regulation of Il22 and increased phosphorylation of signal transducer and activator of transcription 3 (STAT3) as part of the mucosal inflammatory response to Clostridium difficile infection in mice. Others have shown that phosphorylation of STAT3 at mucosal surfaces includes interleukin‐22 (IL‐22) and CD160‐mediated components. The current study sought to determine the potential role(s) of IL‐22 and/or CD160 in the mucosal response to C. difficile infection. Clostridium difficile‐infected mice treated with anti‐IL‐22, anti‐CD160 or a combination of the two showed significantly reduced STAT3 phosphorylation in comparison to C. difficile‐infected mice that had not received either antibody. In addition, C. difficile‐infected mice treated with anti‐IL‐22/CD160 induced a smaller set of genes, and at significantly lower levels than the untreated C. difficile‐infected mice. The affected genes included pro‐inflammatory chemokines and cytokines, and anti‐microbial peptides. Furthermore, histopathological and flow cytometric assessments both showed a significantly reduced influx of neutrophils in C. difficile‐infected mice treated with anti‐IL‐22/CD160. These data demonstrate that IL‐22 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 IL‐22 and CD160 in mediating both the pro‐inflammatory and pro‐survival aspects of the host mucosal response in this infection.