A specific role for TLR1 in protective T(H)17 immunity during mucosal infection.
A specific role for TLR1 in protective T(H)17 immunity during mucosal infection.
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DOI：
10.1084/jem.20112339
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发表时间：
2012-07-30
期刊：
影响因子：
--
通讯作者：
Jabri B
中科院分区：
文献类型：
--
作者：
DePaolo RW;Kamdar K;Khakpour S;Sugiura Y;Wang W;Jabri B
TLR 1/TLR 2复合物是诱导IL-6和IL-23产生保护性TH 17介导的免疫和伊加产生所必需的，在口服而非全身性小肠结肠炎耶尔森氏菌感染后。调节性免疫应答和炎症性免疫应答之间的平衡对于维持肠道内稳态至关重要。此外，炎症反应的性质需要根据组织进行调整，以提供适当的保护性免疫，同时保持宿主的完整性。TLR 2（Toll样受体2）是一种独特的TLR，因为它已被证明可以促进调节性和炎症性T细胞应答。使用小肠结肠炎耶尔森氏菌，我们表明，口腔感染促进TH 17免疫，而全身感染促进TH 1免疫。此外，口腔感染期间TH 17免疫的诱导依赖于TLR 1，并且是由TLR 2/TLR 1诱导的IL-6和IL-23的组合效应以及肠环境中TGF-β的存在引起的。有趣的是，TLR 2/TLR 1在全身感染期间不参与TH 1免疫应答，而TLR 2/TLR 6受体复合物在全身和口腔感染期间诱导IL-10+调节性T细胞应答。我们的研究结果表明，感染途径是决定哪些途径提供保护性免疫的核心。此外，他们还证明了TLR 2在肠道中具有双重免疫功能，并将TLR 1鉴定为保护性肠道TH 17免疫的关键先天受体。
TLR1/TLR2 complexes are required for induction of IL-6 and IL-23 to generate protective TH17-mediated immunity and IgA production after oral but not systemic Yersinia enterocolitica infection. The balance between regulatory and inflammatory immune responses is critical to maintain intestinal homeostasis. Furthermore, the nature of the inflammatory response needs to be tailored to the tissue to provide proper protective immunity while preserving host integrity. TLR2 (Toll-like receptor 2) is a unique TLR in that it has been shown to promote regulatory and inflammatory T cell responses. Using Yersinia enterocolitica, we show that oral infection promotes TH17 immunity, whereas systemic infection promotes TH1 immunity. Furthermore, induction of TH17 immunity during oral infection is dependent on TLR1 and results from the combinatorial effect of TLR2/TLR1-induced IL-6 and IL-23 and the presence of TGF-β in the intestinal environment. Interestingly, TLR2/TLR1 was not involved in TH1 immune responses during systemic infection, whereas the TLR2/TLR6 receptor complex induced IL-10+ regulatory T cell responses during both systemic and oral infections. Our results reveal that the route of infection is central in determining which pathways provide protective immunity. Furthermore, they also demonstrate that TLR2 has dual immune functions in the gut and identify TLR1 as a critical innate receptor for protective intestinal TH17 immunity.
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32.4
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影响因子：
30.3
作者：
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通讯作者：
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