IL–17 receptor signaling regulates Citrobacter rodentium growth

Abstract

Abstract The type 17 cytokine receptors are thought to play critical roles in mucosal immunity. We have shown that intestinal epithelial expression of IL–17 receptor control the development of microbiota in the terminal ileum and conditional deletion of these receptors results in overgrowth of segmented filamentous bacteria. To study the roles of these receptors in response to an attaching and effacing pathogen we challenged intestinal specific Il17ra mice and Il17rc mice with Citrobacter rodentium (C. rodentium). Conditional deletion of Il17ra and l17rc Iresulted in increased bacterial growth in the colon as well as enhanced dissemination to the liver suggesting that intestinal epithelial IL–17 receptors expression is required for control of this infection. This was supported by unbiased RNAseq analysis of the colon that showed diminished expression of Pigr, Tnfsf13 and Nox1 in the absence of Il17ra. IgA has crucial role in mucosal immunity to protect from pathogenic bacteria. PIGR binds dimeric IgA and translocation into lumen, while TNFSF13 activates induce differentiation to plasma cells following–crass switch. C. rodentium specific IgA in stool and C. rodentium specific IgA producing cells in lamina propria were reduced in Il17ra mice. These results suggested IL-17 receptor signaling regulates transcytosis of C. rodentium specific IgA as well as secretion of bacteria specific IgA. On the other hands Nox1 can produce apical hydrogen peroxide. Nox1 null mice were more sensitive for C. rodentium infection. Furthermore Nox1 was expressed by IL–17A stimulation in colonic organoid. Taken together, IL–17 receptor signaling control to produce C. rodentium specific IgA through PIGR and TNFSF13 as well as hydrogen peroxide through NOX1.