Mazmanian Sarkis K, Liu Cui Hua, Tzianabos Arthur O, Kasper Dennis L
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell. 2005 Jul 15;122(1):107-18. doi: 10.1016/j.cell.2005.05.007.
The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show 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 immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.
哺乳动物的胃肠道拥有一个复杂的生态系统，由无数与宿主免疫系统保持平衡的细菌组成。在进化过程中形成的这种共生关系具有互利共生的潜力。然而，介导共生的细菌分子的身份仍不明确。在这里，我们表明，在用无处不在的肠道微生物脆弱拟杆菌对动物进行定殖的过程中，一种细菌多糖（PSA）指导发育中的免疫系统的细胞和物理成熟。与无菌动物的比较表明，脆弱拟杆菌定殖期间PSA的免疫调节活性包括纠正全身性T细胞缺陷和T（H）1/T（H）2失衡以及指导淋巴器官发生。脆弱拟杆菌的PSA突变体不能恢复这些免疫功能。肠道树突状细胞呈递的PSA激活CD4+T细胞并引发适当的细胞因子产生。这些发现为宿主-细菌共生提供了分子基础，并揭示了介导宿主免疫系统发育的共生细菌的原型分子。
