Parkin Impairs Antiviral Immunity by Suppressing the Mitochondrial Reactive Oxygen Species-Nlrp3 Axis and Antiviral Inflammation
Jian Li,
Chunmei Ma,
Fei Long,
Dongxue Yang,
Xue Liu,
Yingchao Hu,
Chunyan Wu,
Bingwei Wang,
Min Wang,
Yunzi Chen,
Genyan Liu,
Paul N. Moynagh,
Jiawei Zhou,
Tao Peng,
Shuo Yang
Affiliations
Jian Li
Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
Chunmei Ma
Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
Fei Long
Laboratory of Viral Immunology, State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, China
Dongxue Yang
Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
Xue Liu
Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
Yingchao Hu
Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
Chunyan Wu
Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
Bingwei Wang
Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, China
Min Wang
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Yunzi Chen
Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
Genyan Liu
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Paul N. Moynagh
Maynooth University Human Health Research Institute, Department of Biology, National University of Ireland Maynooth, Maynooth, Ireland; Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK
Jiawei Zhou
Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Tao Peng
Laboratory of Viral Immunology, State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, China; Corresponding author
Shuo Yang
Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; Corresponding author
Summary: 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. : Biological Sciences; Biochemistry; Genetics; Molecular Biology; Immunology; Cell Biology Subject Areas: Biological Sciences, Biochemistry, Genetics, Molecular Biology, Immunology, Cell Biology
