CD14 controls the LPS-induced endocytosis of Toll-like receptor 4.
CD14 controls the LPS-induced endocytosis of Toll-like receptor 4.
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CD14控制着LPS引起的Toll样受体4的内吞作用。
DOI：
10.1016/j.cell.2011.09.051
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发表时间：
2011-11-11
期刊：
影响因子：
64.5
通讯作者：
Kagan JC
中科院分区：
文献类型：
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作者：
Zanoni I;Ostuni R;Marek LR;Barresi S;Barbalat R;Barton GM;Granucci F;Kagan JC
Toll样受体(Toll-like Receptor，TLRs)转运到各种细胞器已成为调节天然免疫的重要途径。虽然我们的大部分知识仅限于促进新合成受体转运的调控因子，但在微生物检测后控制TLR转运的调控因子仍不清楚。在这里，我们报告了质膜上定位的模式识别受体(PRR)CD14是微生物诱导的TLR4内吞作用所必需的。在树突状细胞中，这种依赖CD14的内吞作用途径在暴露于炎症介质时上调。我们发现酪氨酸激酶Syk及其下游效应蛋白γ2是TLR4内吞作用和信号转导的重要调节因子。这些数据证实，在微生物检测时，上游PRR(CD14)控制下游PRR(TLR4)的运输和信号传递功能。这种先天免疫传递级联说明了病原体检测系统是如何工作来诱导膜运输和信号转导的。
The transport of Toll-like Receptors (TLRs) to various organelles has emerged as an essential means by which innate immunity is regulated. While most of our knowledge is restricted to regulators that promote the transport of newly synthesized receptors, the regulators that control TLR transport after microbial detection remain unknown. Here, we report that the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4. In dendritic cells, this CD14-dependent endocytosis pathway is upregulated upon exposure to inflammatory mediators. We identify the tyrosine kinase Syk and its downstream effector PLCγ2 as important regulators of TLR4 endocytosis and signaling. These data establish that upon microbial detection, an upstream PRR (CD14) controls the trafficking and signaling functions of a downstream PRR (TLR4). This innate immune trafficking cascade illustrates how pathogen detection systems operate to induce both membrane transport and signal transduction.
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影响因子：
64.8
作者：
Hoebe, K;Georgel, P;Beutler, B
通讯作者：
Beutler, B
影响因子：
30.5
作者：
Hamerman, JA;Tchao, NK;Lanier, LL
通讯作者：
Lanier, LL
影响因子：
64.5
作者：
Dixit E;Boulant S;Zhang Y;Lee AS;Odendall C;Shum B;Hacohen N;Chen ZJ;Whelan SP;Fransen M;Nibert ML;Superti-Furga G;Kagan JC
通讯作者：
Kagan JC
影响因子：
7.3
作者：
Depoil, David;Weber, Michele;Batista, Facundo D.
通讯作者：
Batista, Facundo D.
DOI：
10.1038/nri2587
发表时间：
2009-08
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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