Activation of p38? in T cells regulates the intestinal host defense against attaching and effacing bacterial infections.

ABSTRACT: Intestinal infections by attaching and effacing (A/E) bacterial pathogens cause severe colitis and bloody diarrhea. Although p38? in intestinal epithelial cells (IEC) plays an important role in promoting protection against A/E bacteria by regulating T cell recruitment, its impact on immune responses remains unclear. In this study, we show that activation of p38? in T cells is critical for the clearance of the A/E pathogen Citrobacter rodentium. Mice deficient of p38? in T cells, but not in macrophages or dendritic cells, were impaired in clearing C. rodentium. Expression of inflammatory cytokines such as IFN-? by p38?-deficient T cells was reduced, which further reduced the expression of inflammatory cytokines, chemokines, and antimicrobial peptide by IECs and led to reduced infiltration of T cells into the infected colon. Administration of IFN-? activated the mucosal immunity to C. rodentium infection by increasing the expression of inflammation genes and the recruitment of T cells to the site of infection. Thus, p38? contributes to host defense against A/E pathogen infection by regulating the expression of inflammatory cytokines that activate host defense pathways in IECs.

SUBMITTER: Shim EJ 

PROVIDER: S-EPMC3770349 | biostudies-other | 2013 Sep

REPOSITORIES: biostudies-other