IL-27/IL-27 Receptor Signaling Provides Protection in Clostridium difficile-Induced Colitis

Abstract

Background. Clostridium difficile is a leading cause of nosocomial infection. The role of cytokine interleukin-27 (IL-27) in the immunopathology of C. difficile infection (CDI) remains unknown. Methods. The production of IL-27 was determined in human and murine CDI. Furthermore, wild-type (WT) and IL-27 receptor-deficient (WSX-1-/-) mice were treated with an antibiotic mixture and infected with C. difficile to investigate the effects of IL-27 on host response to CDI. Results. IL-27 production was elevated during CDI in humans and mice. Infected WSX-1-/-mice experienced increased weight loss, enhanced colonic histology damage, less C. difficile clearance, and decreased survival compared to WT controls during CDI. IL-27 administration reduced CDI-associated mortality and tissue pathology with improved C. difficile clearance in WT mice after C. difficile challenge. Mechanistically, IL-27-mediated host defense against CDI was associated with downregulation of IL-17A and IL-23, but upregulation of IL-10 and interferon-gamma during CDI. Conclusions. Our data suggest a previously unrecognized role for IL-27 in the pathogenesis of CDI, potentially providing new insight for IL-27-mediated protection against C. difficile-induced pathology.