| First Author | McDermott AJ | Year | 2017 |
| Journal | Immunology | Volume | 150 |
| Issue | 4 | Pages | 468-477 |
| PubMed ID | 27995603 | Mgi Jnum | J:246725 |
| Mgi Id | MGI:5922358 | Doi | 10.1111/imm.12700 |
| Citation | McDermott AJ, et al. (2017) Role of interferon-gamma and inflammatory monocytes in driving colonic inflammation during acute Clostridium difficile infection in mice. Immunology 150(4):468-477 |
| abstractText | The inflammatory response to the colonic pathogen Clostridium difficile is characterized by the induction of inflammatory cytokines including Interleukin-23 (IL-23) and interferon-gamma (IFN-gamma) and the recruitment of myeloid cells including Ly6CHigh monocytes. IL-23 knockout mice showed reduced expression of the monocyte chemokines Ccl4 and Ccl7, but not Ccl2, as well as reduced Ly6CHigh Ly6GMid monocyte recruitment to the colon in response to C. difficile colitis. Clostridium difficile-infected CCR2-/- (CCR2 KO) mice showed a significant defect in Ly6CHigh Ly6GMid monocyte recruitment to the colon in response to C. difficile. Although there was no decrease in expression of the inflammatory cytokines Il1b, Il6 or Tnf or reduction in the severity of colonic histopathology associated with ablation of monocyte recruitment, Slpi and Inos expression was significantly reduced in the colons of these animals. Additionally, neutralization of IFN-gamma through the administration of anti-IFN-gamma monoclonal antibody resulted in a significant reduction in the expression of the IFN-gamma-inducible chemokines Cxcl9 and Cxcl10, but not a reduction in the neutrophil chemokines Cxcl1, Cxcl2 and Ccl3 or the monocyte chemokine Ccl2. Consistently, monocyte and neutrophil recruitment were unchanged following anti-IFN-gamma treatment. Additionally, Inos and Slpi expression were unchanged following anti-IFN-gamma treatment, suggesting that Inos and Slpi regulation is independent of IFN-gamma during C. difficile colitis. Taken together, these data strongly suggest that IL-23 and CCR2 signalling are required for monocyte recruitment during C. difficile colitis. Additionally, these studies also suggest that monocytes, but not IFN-gamma, are necessary for full expression of Inos and Slpi in the colon. |
