Division of Bacterial Infection Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.
PLoS Pathog. 2013;9(6):e1003409. doi: 10.1371/journal.ppat.1003409. Epub 2013 Jun 6.
NF-κB plays a central role in modulating innate immune responses to bacterial infections. Therefore, many bacterial pathogens deploy multiple mechanisms to counteract NF-κB activation. The invasion of and subsequent replication of Shigella within epithelial cells is recognized by various pathogen recognition receptors as pathogen-associated molecular patterns. These receptors trigger innate defense mechanisms via the activation of the NF-κB signaling pathway. Here, we show the inhibition of the NF-κB activation by the delivery of the IpaH E3 ubiquitin ligase family member IpaH0722 using Shigella's type III secretion system. IpaH0722 dampens the acute inflammatory response by preferentially inhibiting the PKC-mediated activation of NF-κB by ubiquitinating TRAF2, a molecule downstream of PKC, and by promoting its proteasome-dependent degradation.
NF-κB 在调节对细菌感染的先天免疫反应中起着核心作用。因此，许多细菌病原体部署多种机制来对抗 NF-κB 的激活。志贺氏菌在肠上皮细胞内的入侵和随后的复制被各种病原体识别受体识别为病原体相关分子模式。这些受体通过 NF-κB 信号通路的激活触发先天防御机制。在这里，我们展示了使用志贺氏菌的 III 型分泌系统传递 IpaH E3 泛素连接酶家族成员 IpaH0722 抑制 NF-κB 激活。IpaH0722 通过泛素化 PKC 下游的 TRAF2 并促进其蛋白酶体依赖性降解，优先抑制 PKC 介导的 NF-κB 的激活，从而抑制急性炎症反应。
