Commensal bacteria contribute to immune homeostasis in the gastrointestinal tract; however, the underlying mechanisms for this are not well understood. A single dose of exopolysaccharide (EPS) from the probiotic spore-forming bacterium Bacillus subtilis protects mice from acute colitis induced by the enteric pathogen Citrobacter rodentium. Adoptive transfer of macrophage-rich peritoneal cells from EPS-treated mice confers protection from disease to recipient mice. In vivo, EPS induces development of anti-inflammatory M2 macrophages in a TLR4-dependent manner, and these cells inhibit T cell activation in vitro and in C. rodentium–infected mice. In vitro, M2 macrophages inhibit CD4+ and CD8+ T cells. The inhibition of CD4+ T cells is dependent on TGF-β, whereas inhibition of CD8+ T cells is dependent on TGF-β and PD-L1. We suggest that administration of B. subtilis EPS can be used to broadly inhibit T cell activation and, thus, control T cell–mediated immune responses in numerous inflammatory diseases.
This work was supported by National Institutes of Health Grants R21AI098187, R01AI110586, R01AI050260, and F31DK104541.
Abbreviations used in this article:
- day postinfection
- dextran sulfate sodium
- experimental autoimmune encephalomyelitis
- inflammatory bowel disease
- inducible regulatory T cell
- mesenteric lymph node
- polysaccharide A
- Received September 21, 2016.
- Accepted January 19, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.