Enhancement of Reactive Oxygen Species Production and Chlamydial Infection by the Mitochondrial Nod-like Family Member NLRX1

Enhancement of Reactive Oxygen Species Production and Chlamydial Infection by the Mitochondrial Nod-like Family Member NLRX1
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DOI:
10.1074/jbc.m110.137885
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发表时间:
2010-12-31
影响因子:
4.8
通讯作者:
Ojcius, David M.
Ojcius, David M.
中科院分区:
生物学2区
文献类型:
--
作者:
Abdul-Sater, Ali A.;Said-Sadier, Najwane;Ojcius, David M.

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沙眼衣原体感染会造成严重和不可逆转的损害,可导致男性和女性不育和失明。在上皮细胞感染后,衣原体诱导活性氧(ROS)的产生。非常规地,衣原体通过激活半胱天冬酶-1来利用ROS,这有助于衣原体生长。NLRX 1是Nod样受体家族的一员,可易位至线粒体,可增加福氏志贺菌感染后线粒体的ROS产生。然而,一般来说,ROS也可以由膜结合的NADPH氧化酶产生。鉴于ROS诱导的caspase-1活化在衣原体空泡生长中的重要性,我们研究了衣原体感染后上皮细胞中ROS产生的来源。沙眼在这项研究中,我们提供的证据表明,在衣原体感染期间由NADPH氧化酶产生的基础水平的ROS,但ROS水平,无论其来源,是由NLRX 1依赖性机制增强。值得注意的是,NLRX 1的存在是衣原体最佳生长所必需的。
Chlamydia trachomatis infections cause severe and irreversible damage that can lead to infertility and blindness in both males and females. Following infection of epithelial cells, Chlamydia induces production of reactive oxygen species (ROS). Unconventionally, Chlamydiae use ROS to their advantage by activating caspase-1, which contributes to chlamydial growth. NLRX1, a member of the Nod-like receptor family that translocates to the mitochondria, can augment ROS production from the mitochondria following Shigella flexneri infections. However, in general, ROS can also be produced by membrane-bound NADPH oxidases. Given the importance of ROS-induced caspase-1 activation in growth of the chlamydial vacuole, we investigated the sources of ROS production in epithelial cells following infection with C. trachomatis. In this study, we provide evidence that basal levels of ROS are generated during chlamydial infection by NADPH oxidase, but ROS levels, regardless of their source, are enhanced by an NLRX1-dependent mechanism. Significantly, the presence of NLRX1 is required for optimal chlamydial growth.