A Paradigm for Commensalism: The Role of a Specific Microbial Polysaccharide in Health and Disease
The human gastrointestinal tract is colonized by 100 trillion microorganisms, including both beneficial and potentially pathogenic species. A zwitterionic polysaccharide (PSA) from the gastrointestinal microorganism Bacteroides fragilis has been shown to be the archetypal molecule of commensal bacteria that mediates development of the host immune system. PSA stimulates the normal balance of Th1 and Th2 CD4+ T cells and can correct histologic defects in the spleen and thymus of germ-free mice. PSA stimulates the innate immune system as a ligand for Toll-like receptor 2 and thereby promotes interactions with the adaptive immune system that are required for T-cell activation. PSA protects animals from colitis induced by Helicobacter hepaticus, a commensal with pathogenic potential. In animals harboring a B. fragilis mutant that does not express PSA, H. hepaticus colonization leads to disease and proinflammatory cytokine production in colonic tissues. Purified PSA administered to animals suppresses the production of the proinflammatory cytokine interleukin-17 by intestinal immune cells. PSA protects animals from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. Thus polysaccharides of the bacterial microbiota can mediate the critical balance between health and disease in the host. As evidence accumulates, this concept is being accepted as an important feature of the immune repertoire.