Capsular polysaccharides of symbiotic bacteria modulate immune responses during experimental colitis

Abstract

The mammalian gastrointestinal tract harbors a complex ecosystem consisting of extraordinary numbers of resident bacteria in homeostasis with the host immune system. Here we demonstrate that during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the novel immunomodulatory activities of PSA during B fragilis colonization include correcting T cell deficiencies and T_H1/T_H2 imbalances, as well as directing lymphoid organogenesis. The mechanism of PSA activity requires antigen endocytosis by intestinal dendritic cells and presentation by major histocompatibility class II to signal CD4⁺ T cell activation and cytokine production. Most significant, the benefit of this process for the host is demonstrated by PSA-conferred protection against experimental colitis induced by pathogenic bacteria.