An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system

Cell, Vol. 122, 107-118, 2005

Speaker：Jung-yen Liu                    Time：2006/02/22

Commentator：Dr. Lien-I Hor              Place：Room 601

Abstract：

Our gut is home to several hundreds of species of bacteria, which live peacefully with our immune system. It has long been known that the germ-free mice, which have no commensal microflora, have defects in their immune systems and that introduction of gut flora corrects these defects. However, the exact bacterial determinants are not completely understood. The authors found that germ-free mice are characterized by a decreased number of CD4 T cells in the spleen and by an abnormal organization of the spleen. These defects were corrected after colonization with gut flora Bacteroides fragilis, but not with mutant type of B. fragilis lacking bacterial polysaccharide, PSA. Consistent with this, germ-free mice given with purified PSA developed normal splenic CD4 T cell numbers and splenic organization. They further investigated the molecular mechanism of the restoration of CD4 T cells by PSA. PSA is specifically presented by dendritic cells, with subsequent cell activation. Besides, the activated dendritic cells drive CD4 T cells differentiate into TH1 cells through the IL-12/Stat4 pathway and drive them elicit appropriate cytokine to correct TH1/TH2 imbalances. In a word, this is the first study to show a specific bacterial polysaccharide, PSA, is important for the development of host immune system.

References:

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

2.   Mowat, A.M. Anatomical basis of tolerance and immunity to intestinal antigens. Nat. Rev. Immunol. 3, 331–341 (2003)