Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Cell Microbiol. 2012 Oct;14(10):1568-83. doi: 10.1111/j.1462-5822.2012.01822.x. Epub 2012 Jun 21.
Members of the NLR family evolved as intracellular sensors for bacterial and viral infection. However, our knowledge on the implication of most of the human NLR proteins in innate immune responses still remains fragmentary. Here we characterized the role of human NLRP10 in bacterial infection. Our data revealed that NLRP10 is a cytoplasmic localized protein that positively contributes to innate immune responses induced by the invasive bacterial pathogen Shigella flexneri. SiRNA-mediated knock-down studies showed that NLRP10 contributes to pro-inflammatory cytokine release triggered by Shigella in epithelial cells and primary dermal fibroblasts, by influencing p38 and NF-κB activation. This effect is dependent on the ATPase activity of NLRP10 and its PYD domain. Mechanistically, NLRP10 interacts with NOD1, a NLR that is pivotally involved in sensing of invasive microbes, and both proteins are recruited to the bacterial entry point at the plasma membrane. Moreover, NLRP10 physically interacts with downstream components of the NOD1 signalling pathway, such as RIP2, TAK1 and NEMO. Taken together, our data revealed a novel role of NLRP10 in innate immune responses towards bacterial infection and suggest that NLRP10 functions as a scaffold for the formation of the NOD1-Nodosome.
NLR 家族成员作为细胞内细菌和病毒感染的感应器而进化。然而，我们对于大多数人类 NLR 蛋白在先天免疫反应中的影响的了解仍然是零散的。在这里，我们描述了人类 NLRP10 在细菌感染中的作用。我们的数据揭示了 NLRP10 是一种细胞质定位的蛋白，它积极地有助于由侵袭性细菌病原体福氏志贺菌诱导的先天免疫反应。siRNA 介导的敲低研究表明，NLRP10 通过影响 p38 和 NF-κB 的激活，有助于上皮细胞和原代真皮成纤维细胞中由 Shigella 触发的促炎细胞因子的释放。这种效应依赖于 NLRP10 的 ATP 酶活性及其 PYD 结构域。在机制上，NLRP10 与 NOD1 相互作用，NOD1 是参与感应侵袭性微生物的关键 NLR，并且这两种蛋白都被募集到质膜上的细菌进入点。此外，NLRP10 与 NOD1 信号通路的下游成分，如 RIP2、TAK1 和 NEMO，相互作用。总之，我们的数据揭示了 NLRP10 在针对细菌感染的先天免疫反应中的新作用，并表明 NLRP10 作为 NOD1-Nodosome 形成的支架发挥作用。
