Parkin Impairs Antiviral Immunity by Suppressing the Mitochondrial Reactive Oxygen Species-NIrp3 Axis and Antiviral Inflammation
Parkin Impairs Antiviral Immunity by Suppressing the Mitochondrial Reactive Oxygen Species-NIrp3 Axis and Antiviral Inflammation
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Parkin 通过抑制线粒体活性氧 Nlrp3 轴和抗病毒炎症来损害抗病毒免疫
DOI：
10.1016/j.isci.2019.06.008
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发表时间：
2019-06-28
期刊：
影响因子：
5.8
通讯作者：
Yang, Shuo
中科院分区：
文献类型：
--
作者：
Li, Jian;Ma, Chunmei;Yang, Shuo
虽然线粒体被认为是参与宿主防御病毒感染，线粒体自噬，维持线粒体稳态的重要机制，在抗病毒免疫的生理作用仍然不清楚。在这里，我们表明，帕金，在线粒体自噬的核心球员，在调节宿主的抗病毒反应具有重要的功能。帕金森基因敲除小鼠在病毒感染后表现出改善的病毒清除和存活率。然而，帕金缺乏症不影响抗病毒信号和干扰素的产生。相反，帕金缺乏症通过增强线粒体ROS（mtROS）介导的NLRP 3炎性小体激活和促进病毒清除来增强先天性抗病毒炎症。NLRP 3的缺失可以逆转Parkin敲除小鼠中增强的抗病毒应答。此外，我们发现，在病毒感染患者的外周血单个核细胞中，Parkin表达下调。总的来说，我们的研究结果表明，帕金通过控制mtROS-NLRP 3轴介导的炎症在抗病毒免疫中发挥重要作用。这些发现提供了生理学上的重要性，线粒体自噬调节宿主的抗病毒反应。
Although mitochondria are known to be involved in host defense against viral infection, the physiological role of mitophagy, a crucial mechanism for maintaining mitochondrial homeostasis, in antiviral immunity remains poorly defined. Here, we show that Parkin, a central player in mitophagy, has a vital function in regulating host antiviral responses. Parkin-knockout mice exhibit improved viral clearance and survival after viral infection. However, Parkin deficiency does not affect antiviral signaling and interferon production. Instead, Parkin deficiency augments innate antiviral inflammation by enhancing mitochondrial ROS (mtROS)-mediated NLRP3 inflammasome activation and promoting viral clearance. Loss of NLRP3 can reverse the enhanced antiviral responses in Parkin knockout mice. Furthermore, we find that Parkin expression is downregulated in peripheral blood mononuclear cells of patients infected with virus. Collectively, our results suggest that Parkin plays an important role in antiviral immunity by controlling mtROS-NLRP3 axis-mediated inflammation. These findings provide physiological insight of the importance of mitophagy in regulating host antiviral response.