LRRK2 promotes the activation of NLRC4 inflammasome during Salmonella Typhimurium infection
Year: 2017
Type: article
Abstract: Although genetic polymorphisms in the LRRK2 gene are associated with a variety of diseases, the physiological function of LRRK2 remains poorly understood. In this study, we report a crucial role for LRRK2 in the activation of the NLRC4 inflammasome during host defense against Salmonella enteric serovar Typhimurium infection. LRRK2 deficiency reduced caspase-1 activation and IL-1β secretion in response to NLRC4 inflammasome activators in macrophages. Lrrk2−/− mice exhibited impaired clearance of pathogens after acute S. Typhimurium infection. Mechanistically, LRRK2 formed a complex with NLRC4 in the macrophages, and the formation of the LRRK2–NLRC4 complex led to the phosphorylation of NLRC4 at Ser533. Importantly, the kinase activity of LRRK2 is required for optimal NLRC4 inflammasome activation. Collectively, our study reveals an important role for LRRK2 in the host defense by promoting NLRC4 inflammasome activation.
DOI: 10.1084/jem.20170014
Authors: Weiwei Liu, Xia’nan Liu, Yu Li, Junjie Zhao, Zhenshan Liu, Zhuqin Hu, Ying Wang, Yufeng Yao, Aaron W. Miller, Bing Su, Mark R. Cookson, Xiaoxia Li, Zizhen Kang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: Michael J. Fox Foundation for Parkinson's Research, National Natural Science Foundation of China, China Postdoctoral Science Foundation, Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, National Heart, Lung, and Blood Institute, National Cancer Institute
OpenAlex ID: W2748076679