Mechanism by which commensal bacteria limit inflammation (MUC4P.844)

Abstract Trillions of bacteria live in homeostasis within the gastrointestinal tract and provide a variety of benefits to the host immune system. One beneficial function of the healthy microbiota is to protect the host from enteric pathogens; however, little is known about the mechanisms by which this occurs. We utilize a mouse model in which a single dose of the commensal bacterium, Bacillus subtilis, protects mice from disease induced by the enteric pathogen Citrobacter rodentium. Our goal is to elucidate the mechanism by which B. subtilis protects from inflammation caused by infection with C. rodentium. We identified exopolysaccharides (EPS) to be the active molecule of B. subtilis, and a single i.p. dose of EPS protects mice from infection. Because protection occurs within a few days, we hypothesized that EPS elicits a protective response by modulating the innate immune system. EPS binds F4/80+CD11b+ peritoneal macrophages, and after i.p. injection of EPS, we identified F4/80+CD11b+ cells that are MHCII+CD206+, indicative of alternatively activated macrophages. We further show that peritoneal macrophages from EPS-treated mice suppress T cell proliferation in vitro, suggesting that these cells contribute to EPS mediated protection from inflammation. We are testing if these cells differentiate in the peritoneum following EPS treatment and whether they mediate protection from C. rodentium induced inflammation.