| First Author | Stange J | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 5 | Pages | 2410-8 |
| PubMed ID | 22266282 | Mgi Jnum | J:181287 |
| Mgi Id | MGI:5310697 | Doi | 10.4049/jimmunol.1102062 |
| Citation | Stange J, et al. (2012) IL-22 Mediates Host Defense against an Intestinal Intracellular Parasite in the Absence of IFN-gamma at the Cost of Th17-Driven Immunopathology. J Immunol 188(5):2410-8 |
| abstractText | The roles of Th1 and Th17 responses as mediators of host protection and pathology in the intestine are the subjects of intense research. In this study, we investigated a model of intestinal inflammation driven by the intracellular apicomplexan parasite Eimeria falciformis. Although IFN-gamma was the predominant cytokine during E. falciformis infection in wild-type mice, it was found to be dispensable for host defense and the development of intestinal inflammation. E. falciformis-infected IFN-gammaR(-/-) and IFN-gamma(-/-) mice developed dramatically exacerbated body weight loss and intestinal pathology, but they surprisingly harbored fewer parasites. This was associated with a striking increase in parasite-specific IL-17A and IL-22 production in the mesenteric lymph nodes and intestine. CD4(+) T cells were found to be the source of IL-17A and IL-22, which drove the recruitment of neutrophils and increased tissue expression of anti-microbial peptides (RegIIIbeta, RegIIIgamma) and matrix metalloproteinase 9. Concurrent neutralization of IL-17A and IL-22 in E. falciformis-infected IFN-gammaR(-/-) mice resulted in a reduction in infection-induced body weight loss and inflammation and significantly increased parasite shedding. In contrast, neutralization of IL-22 alone was sufficient to increase parasite burden, but it had no effect on body weight loss. Treatment of an E. falciformis-infected intestinal epithelial cell line with IFN-gamma, IL-17A, or IL-22 significantly reduced parasite development in vitro. Taken together, to our knowledge these data demonstrate for the first time an antiparasite effect of IL-22 during an intestinal infection, and they suggest that IL-17A and IL-22 have redundant roles in driving intestinal pathology in the absence of IFN-gamma signaling. |
