Intestinal epithelial cells contribute to Citrobacter rodentium induced infectious colitis through an NF-κB-dependent mechanism (MUC2P.826)

Abstract

Abstract Exposing mice to a psychological stressor during challenge with the enteric pathogen Citrobacter rodentium (Cr) exacerbates Cr-induced infectious colitis. Enhanced recruitment of inflammatory monocytes to the colon, via a CCL2-dependent mechanism, is essential for the exacerbation of infectious colitis by stressor exposure, however the cell type responsible for the increase of colonic CCL2 is unknown. Previous evidence demonstrates that Cr-induced CCL2 is through an NF-κB mediated mechanism, thus this study was designed to test the hypothesis that NF-κB-derived gene expression from intestinal epithelial cells is necessary for the exacerbation of colitis via the recruitment of inflammatory monocytes, as well as the corollary hypothesis that inflammatory monocytes contribute to infectious colitis also via NF-κB activation. To test these hypotheses, two different strains of mice were challenged with Cr in which classical NF-κB activation is defective via the deletion of IKKβ in either intestinal epithelial cells (IKKβΔIEC) or myeloid-derived cells (IKKβΔMY). There was a reduction in Cr-induced colon mass, colonic histopathology, and colonic inflammatory mediator gene expression in IKKβΔIEC mice as compared to wild type controls. In addition, Cr-induced colon mass, histopathology, and colonic gene expression is further reduced in IKKβΔMY mice. Together, these data illustrate the deleterious effects of pathogen induced NF-κB activation has during enteric pathogen challenge.