Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling
Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling
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DOI：
10.4049/jimmunol.176.4.2373
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发表时间：
2006-02-15
影响因子：
4.4
通讯作者：
Wetzler, LM
中科院分区：
文献类型：
--
作者：
Massari, P;Visintin, A;Wetzler, LM
TLR2在多种细菌产物启动细胞先天免疫反应中起着关键作用。TLRS信号通路包括TLR2及其辅助受体TLR1和TLR6，由多种特异性配体介导。尽管在过去的几年里，许多TLR介导的细胞信号通路已经被阐明，但导致细胞激活的分子机制仍然知之甚少。在这项研究中，我们研究了脑膜炎奈瑟菌PorB与TLR2的相互作用，并首次描述了细菌蛋白与TLR2的直接结合。使用标记的PorB，我们证明了它在体外以可溶的形式与TLR2结合，以及当它在人胚胎肾脏293细胞表面过表达时。我们还发现TLR2介导的PorB结合与细胞激活直接相关。此外，利用表达嵌合的TLR2/TLR1和TLR2/TLR6复合体的293细胞，我们报告了PorB与TLR2/TLR1异二聚体结合的选择性，这是在转基因293细胞和小鼠B细胞中启动信号所需的。总之，这些数据提供了新的证据，表明TLR2通过直接结合识别PorB，并且PorB诱导的细胞激活是由TLR2/TLR1复合体介导的。免疫学杂志，2006,176：2373-2380。
TLR2 plays a key role in the initiation of the cellular innate immune responses by a wide range of bacterial products. TLRs signaling, including TLR2 and its coreceptors TLR1 and TLR6, is mediated by a number of specific ligands. Although many of the TLR-mediated cell signaling pathways have been elucidated in the past few years, the molecular mechanisms that lead to cell activation are still poorly understood. In this study, we investigate the interaction of PorB from Neisseria meningitidis with TLR2 and describe the direct binding of a bacterial protein to TLR2 for the first time. Using labeled PorB, we demonstrate its binding to TLR2 both in its soluble form in vitro, and when it is over-expressed on the surface of human embryonic kidney 293 cells. We also show that TLR2-mediated binding of PorB is directly related to cellular activation. In addition, using 293 cells expressing the chimeric TLR2/TLR1 and TLR2/TLR6 complexes, we report the selectivity of PorB binding to the TLR2/TLR1 heterodimer, which is required for initiating signaling in transfected 293 cells and in murine B cells. Together, these data provide new evidence that TLR2 recognizes PorB through direct binding, and that PorB-induced cell activation is mediated by a TLR2/TLR1 complex. The Journal of Immunology, 2006, 176: 2373-2380.