Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells

Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells
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DOI:
10.1038/ni1362
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发表时间:
2006-08-01
期刊:
影响因子:
30.5
通讯作者:
Akira, Shizuo
Akira, Shizuo
中科院分区:
医学1区
文献类型:
--
作者:
Uematsu, Satoshi;Jang, Myoung Ho;Akira, Shizuo

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Toll样受体(TLR)识别不同的微生物组分并诱导先天性免疫应答。TLR 5由细菌鞭毛蛋白触发。在这里,我们产生了Tlr 5(-/-)小鼠并评估了体内TLR 5功能。与其他TLR不同,TLR 5在常规树突状细胞或巨噬细胞上不表达。相反,TLR 5主要表达在肠CD 11 c(+)固有层细胞(LPC)上。CD 11 c(+)LPCs以TLR 5依赖的方式检测病原菌并分泌促炎细胞因子。然而,CD 11 c + LPCs不表达TLR 4,并且在暴露于细菌后不分泌促炎细胞因子。值得注意的是,在Tlr 5(-/-)小鼠中,致病性鼠伤寒沙门氏菌从肠道到肠系膜淋巴结的转运受损。这些数据表明,CD 11 c(+)LPCs,通过TLR 5,检测并利用肠腔中的致病菌。
Toll-like receptors (TLRs) recognize distinct microbial components and induce innate immune responses. TLR5 is triggered by bacterial flagellin. Here we generated Tlr5(-/-) mice and assessed TLR5 function in vivo. Unlike other TLRs, TLR5 was not expressed on conventional dendritic cells or macrophages. In contrast, TLR5 was expressed mainly on intestinal CD11c(+) lamina propria cells (LPCs). CD11c(+) LPCs detected pathogenic bacteria and secreted proinflammatory cytokines in a TLR5-dependent way. However, CD11c+ LPCs do not express TLR4 and did not secrete proinflammatory cytokines after exposure to a commensal bacterium. Notably, transport of pathogenic Salmonella typhimurium from the intestinal tract to mesenteric lymph nodes was impaired in Tlr5(-/-) mice. These data suggest that CD11c(+) LPCs, via TLR5, detect and are used by pathogenic bacteria in the intestinal lumen.