Allies from Within

Abstract

In general, people coexist peacefully with the innumerable microorganisms that colonize the gut. Some gut microbes, however, are potential pathogens; moreover, inappropriate immune responses directed against gastrointestinal flora may be involved in the pathogenesis of inflammatory bowel diseases (IBDs) such as ulcerative colitis. Mazmanian et al . used a mouse model of IBD in which naïve effector T cells were introduced into immunodeficient mice, along with the bacterium Helicobacter hepaticus , to investigate the hypothesis that IBDs may involve an imbalance between potentially harmful and potentially beneficial commensal bacteria. Co-colonization with the bacterium Bacteroides fragilis protected these mice from colitis, whereas B. fragilis lacking the surface polysaccharide PSA ( B. fragilis ΔPSA) were not protective. Colon cultures revealed increased abundance of pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) in mice with experimental colitis, an increase blocked by colonization with B. fragilis but not B. fragilis ΔPSA. Oral PSA protected against this model of colitis as well--and also against a chemically induced model of colitis. PSA increased expression of the transcript encoding the anti-inflammatory cytokine interleukin-10 (IL-10) in mouse colon and also in cocultures of bone marrow-derived dendritic cells and naïve CD4 + T cells (BMDC-T cell cocultures). PSA decreased production of TNF-α in BMDC-T cell cocultures infected with H. hepaticus , an effect blocked by neutralizing antibodies directed against the IL-10 receptor. Furthermore, such antibodies inhibited the protective effect of PSA in the T cell-transfer model of colitis, and PSA failed to protect against colitis when the naïve effector T cells were derived from mice lacking IL-10. The authors thus conclude that B. fragilis PSA can modulate the inflammatory response associated with H. hepaticus and thereby protect against IBD. Kullberg discusses the results and provides thoughtful commentary. S. K. Mazmanian, J. L. Round, D. L. Kasper, A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453 , 620-625 (2008). [PubMed] M. C. Kullberg, Immunology: Soothing intestinal sugars. Nature 453 , 602-604 (2008). [PubMed]