A microbial symbiosis factor prevents intestinal inflammatory disease

Sarkis K. Mazmanian, June L. Round & Dennis L. Kasper.

Nature. 453, 620-625 (2008)

Speaker: Yi-Hsuan Chen (陳怡璇)                 Time: 14:00~15:00, Oct. 15, 2008

Commentator: Dr. Jiu-Yao Wang (王志堯老師)      Place: Room 601

Abstract:

According to the “hygiene hypothesis”, exposure to infections in early childhood may decrease the risk of allergic and autoimmune disease. It has been shown that both the gastrointestinal and systemic immune responses are deficient in the absence of commensal microorganisms¹, suggesting that the microbiota is important in the development and differentiation of mammalian immune systems. It was also proposed that an imbalance in the normal microbiota is responsible for the inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis. The authors have previously demonstrated that a human commensal bacterium, Bacteroides fragilis, could correct the defect of CD4⁺ T cells in development in the germ-free animals through the expression of polysaccharide A (PSA)¹. In this study, they further investigated the precise anti-inflammatory mechanism performed by B. fragilis. In the CD4⁺CD45Rb T cell transfer model², they found that the wild type B. fragilis, but not the △PSA mutant, protected the animals from colitis induced by Helicobater hepaticusp. Moreover, the administration of purified PSA prevented the Rag^-/- mice supplemented with CD4⁺CD45Rb^high T cells from gut pathological development and pro-inflammatory cytokine expression caused by H. hepaticusp infection. The same effect was observed in trimitrobenzene sulphonic acid (TNBS)-induced colonic inflammation model. A greatly increased transcriptional level of Il10 was observed in the PSA-treated mice which showed reduced inflammation. In the experiments performed in the Il10^-/- mice, they confirmed that the production of IL-10, a potent anti-inflammatory cytokine, is required for PSA-elicited reduction of intestinal immune response. These results constitute the first reported evidence of a symbiotic bacterial molecule that networks with the immune system to coordinate anti-inflammatory responses required for mammalian health.

References:

1.      Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. & Kasper, D. L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005)

2.      Maloy, K. J. et al. CD4⁺CD25⁺ T_R cells suppress innate immune pathology through cytokine-dependent mechanisms. J. Exp. Med. 197, 111–119 (2003)