• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >TLR signalling augments macrophage bactericidal activity through mitochondrial ROS
【24h】

TLR signalling augments macrophage bactericidal activity through mitochondrial ROS

机译：TLR信号通过线粒体ROS增强巨噬细胞的杀菌活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Reactive oxygen species (ROS) are essential components of the innate immune response against intracellular bacteria and it is thought that professional phagocytes generate ROS primarily via the phagosomal NADPH oxidase machinery. However, recent studies have suggested that mitochondrial ROS (mROS) also contribute to mouse macrophage bactericidal activity, although the mechanisms linking innate immune signalling to mitochondria for mROS generation remain unclear. Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly. Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation. ECSIT- and TRAF6-depleted macro-phages have decreased levels of TLR-induced ROS and are significantly impaired in their ability to kill intracellular bacteria. Additionally, reducing macrophage mROS levels by expressing catalase in mitochondria results in defective bacterial killing, confirming the role of mROS in bactericidal activity. These results reveal a novel pathway Unking innate immune signalling to mitochondria, implicate mROS as an important component of antibacterial responses and further establish mitochondria as hubs for innate immune signalling.
机译：活性氧（ROS）是针对细胞内细菌的先天免疫应答的重要组成部分，据认为专业吞噬细胞主要通过吞噬体NADPH氧化酶机制产生ROS。但是，最近的研究表明，尽管将先天免疫信号传导至线粒体以产生mROS的机制尚不清楚，但线粒体ROS（mROS）也有助于小鼠巨噬细胞的杀菌活性。在这里，我们证明了Toll样受体（TLR1，TLR2和TLR4）的子集的参与导致线粒体募集到巨噬细胞吞噬体并增加mROS的产生。该反应涉及TLR信号转导衔接子，肿瘤坏死因子受体相关因子6（TRAF6）易位至线粒体，在此与蛋白ECSIT（Toll途径中进化上保守的信号转导中间体）结合，这与线粒体呼吸链装配有关。与TRAF6的相互作用导致ECSIT泛素化并在线粒体外围富集，从而导致线粒体和细胞ROS生成增加。耗尽ECSIT和TRAF6的巨噬细胞可降低TLR诱导的ROS的水平，并显着削弱其杀死细胞内细菌的能力。此外，通过在线粒体中表达过氧化氢酶来降低巨噬细胞的mROS水平会导致有害的细菌杀伤作用，从而证实了mROS在杀菌活性中的作用。这些结果揭示了一种将先天免疫信号传递给线粒体的新途径，暗示mROS是抗菌反应的重要组成部分，并进一步将线粒体确立为先天免疫信号的枢纽。

著录项

  • 来源
    《Nature》 |2011年第7344期|p.476-480|共5页
  • 作者

    A. Phillip West; Igor E. Brodsky; Christoph Rahner; Dong Kyun Woo; Hediye Erdjument-Bromage; Paul Tempst; Matthew C. Walsh; Yongwon Choi; Gerald S. Shadel; Sankar Ghosh;

  • 作者单位

    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA;

    Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine,Philadelphia, Pennsylvania 19104, USA;

    Departmentof Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520,USA;

    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA;

    Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA;

    Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA;

    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;

    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;

    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA;

    epartment of Microbiology and Immunology,College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号