Outer membrane vesicles of a human commensal mediate immune regulation and disease protection.
Outer membrane vesicles of a human commensal mediate immune regulation and disease protection.
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DOI：
10.1016/j.chom.2012.08.004
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发表时间：
2012-10-18
影响因子：
30.3
通讯作者：
Mazmanian SK
中科院分区：
文献类型：
--
作者：
Shen Y;Giardino Torchia ML;Lawson GW;Karp CL;Ashwell JD;Mazmanian SK
共生细菌通过多种机制影响宿主的健康和免疫力，包括产生免疫调节分子。脆弱拟杆菌产生荚膜多糖（PSA），其诱导调节性T细胞和粘膜耐受。然而，与采用分泌系统的病原体不同，肠道细菌将分子传递给宿主的机制仍然未知。我们发现，脆弱拟杆菌释放PSA的外膜囊泡（OMV），诱导免疫调节作用，防止实验性结肠炎。树突状细胞（DC）通过TLR 2感知OMV相关的PSA，导致调节性T细胞和抗炎细胞因子产生增强。OMV在DC中诱导的信号传导需要生长停滞和DNA损伤诱导蛋白（Gadd 45 α）。用含有PSA的OMV处理的DC预防实验性结肠炎，而Gadd 45 α-/-DC不能促进调节性T细胞应答或抑制促炎细胞因子产生和宿主病理学。这些发现表明，OMV介导的微生物分子的递送可以预防疾病，揭示了微生物群和哺乳动物之间的界间交流机制。
Commensal bacteria impact host health and immunity through various mechanisms, including the production of immunomodulatory molecules. Bacteroides fragilis produces a capsular polysaccharide (PSA), which induces regulatory T cells and mucosal tolerance. However, unlike pathogens, which employ secretion systems, the mechanisms by which commensal bacteria deliver molecules to the host remain unknown. We reveal that Bacteroides fragilis releases PSA in outer membrane vesicles (OMVs) that induce immunomodulatory effects and prevent experimental colitis. Dendritic cells (DCs) sense OMV-associated PSA through TLR2, resulting in enhanced regulatory T cells and anti-inflammatory cytokine production. OMV-induced signaling in DCs requires Growth Arrest and DNA-Damage-Inducible protein (Gadd45α). DCs treated with PSA-containing OMVs prevent experimental colitis, whereas Gadd45α-/- DCs are unable to promote regulatory T cell responses or suppress pro-inflammatory cytokine production and host pathology. These findings demonstrate that OMV-mediated delivery of a commensal molecule prevents disease, uncovering a mechanism of inter-kingdom communication between the microbiota and mammals.
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DOI：
10.1126/science.1195568
发表时间：
2010-12-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lee YK;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
4.4
作者：
Jirmanova, Ludmila;Jankovic, Dragana;Ashwell, Jonathan D.
通讯作者：
Ashwell, Jonathan D.
影响因子：
4.4
作者：
Ochoa-Reparaz, Javier;Mielcarz, Daniel W.;Kasper, Lloyd H.
通讯作者：
Kasper, Lloyd H.
影响因子：
64.5
作者：
Chung H;Pamp SJ;Hill JA;Surana NK;Edelman SM;Troy EB;Reading NC;Villablanca EJ;Wang S;Mora JR;Umesaki Y;Mathis D;Benoist C;Relman DA;Kasper DL
通讯作者：
Kasper DL
细菌效应器设计和功能的常见主题。
影响因子：
30.3
作者：
Galan, Jorge E.
通讯作者：
Galan, Jorge E.