Impact of Interleukin-10 during Bacterial Induced Colitis

Besides the fundamental role of IL-10 in intestinal homeostasis IL-10 is described as a key regulator of pathogen-specific immune responses. However, it is unclear whether intestinal infection interferes with IL-10-mediated homeostasis. In the present study we dissected the function of IL-10 in a mouse model of infectious colitis. BALB/c mice were infected with Citrobacter rodentium – an enteric pathogen that induces colitis with similarities to inflammatory bowel disease. Infected mice showed typical signs of bacterial-induced inflammation including increased colon weight-to-length ratios as well as higher histopathological scores with elevated crypt hyperplasia. Of note, IL-10 expression was upregulated in colonic tissue after infection, especially in CD4⁺ T cells, macrophages, and dendritic cells with a peak 10-14 days post-infection. We first focused on the impact of CD4⁺ T cell-derived IL-10 and infected CD4-Cre/IL10^fl/fl mice with C. rodentium. Interestingly, mice deficient in CD4⁺ T cell-derived IL-10 showed a faster clearance of the bacterial burden, but developed a more severe colitis with increased pathology and crypt hyperplasia compared to infected wild-type mice. Thus, we conclude that CD4⁺ T cell-derived IL-10 is essential for the control of C. rodentium induced colitis. In future experiments we will examine the impact of macrophage- and dendritic cell-derived IL-10 in infectious colitis.