An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system
An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system
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DOI：
10.1016/j.cell.2005.05.007
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发表时间：
2005-07-15
期刊：
影响因子：
64.5
通讯作者：
Kasper, DL
中科院分区：
文献类型：
--
作者：
Mazmanian, SK;Liu, CH;Kasper, DL
哺乳动物胃肠道具有一个复杂的生态系统，该生态系统由宿主免疫系统中无数细菌组成。根据进化的影响，这种伙伴关系具有共生利益的潜力。但是，介导共生的细菌分子的身份仍然不确定。在这里，我们表明，在具有无处不在的肠道微生物菌落脆弱的动物定植期间，细菌多糖（PSA）指导了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，脆弱芽孢杆菌定植期间PSA的免疫调节活性包括校正全身性T细胞缺乏症，T（H）1/T（H）2（H）2失衡和指导淋巴器官。 B. fragilis的PSA突变体不会恢复这些免疫功能。肠树突状细胞提出的PSA激活CD4（+）T细胞，并引起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。
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.