Mechanism by which commensal exopolysaccharides limit inflammation (MUC9P.744)

Abstract

Abstract Trillions of bacteria live within the gastrointestinal tract and are critical for maintaining intestinal homeostasis; however, the mechanisms utilized by specific bacterial molecules to contribute to homeostasis are not well understood. We utilize a mouse model in which a single dose of the probiotic, B. subtilis, protects mice from acute colitis induced by the enteric pathogen C. rodentium. Our goal is to elucidate the mechanism by which B. subtilis prevents inflammation. We identified exopolysaccharides (EPS) to be the active molecule of B. subtilis, and a single dose of EPS protects mice from disease. EPS specifically binds F4/80+CD11b+ peritoneal macrophages (MΦ). Following EPS treatment, these cells increase expression of CD206+Arg1+YM-1+IL-4Rα+ and inhibit T cell activation and proliferation in vitro, indicative of M2 MΦ. CD4+ T cells drive much of the inflammation associated with C. rodentium infection, and we hypothesized that EPS inhibits CD4+ T cell responses in vivo. Accordingly, we measured levels of IFNγ (Th1), IL-17 (Th17), and IL-13 (Th2) in splenic T cells following EPS treatment and found decreased levels of these cytokines. Similarly, mesenteric lymph node from mice orally gavaged with B. subtilis spores produced decreased levels of T cell cytokines in an EPS dependent manner. We hypothesize that EPS-induced M2 MΦ mediate inhibition of CD4+ T cell responses in vivo and further, that these cells mediate protection from acute colitis induced by C. rodentium.