The neuropeptide CGRP enters the macrophage cytosol to suppress the NLRP3 inflammasome during pulmonary infection  

作　　者：Fangrui Zhu Dou Yu Xiwen Qin Yan Qian Juan Ma Weitao Li Qiannv Liu Chunlei Wang Yan Zhang Yi Li Dong Jiang Shuo Wang Pengyan Xia 

机构地区：[1]Department of Immunology,School of Basic Medical Sciences,Peking University,100191 Beijing,China [2]NHC Key Laboratory of Medical Immunology,Peking University,100191 Bejing,China [3]Key Laboratory of Molecular Immunology,Chinese Academy of Medical Sciences,100191 Bejing,China [4]CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,100101 Bejing,China [5]Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,Hubei 430071,China [6]Department of Anesthesiology,Peking University Third Hospital,100191 Beijing,China [7]Department of Sports Medicine,Peking University Third Hospital,100191 Bejing,China [8]Beijing Key Laboratory of Sports Injuries,Institute of Sports Medicine of Peking University,100191 Bejing,China

出　　处：《Cellular & Molecular Immunology》2023年第3期264-276,共13页中国免疫学杂志（英文版）

摘　　要：The NLRP3 inflammasome plays an essential role in resistance to bacterial infection. The nervous system secretes multiple neuropeptides affecting the nervous system as well as immune cells. The precise impact of the neuropeptide CGRP on NLRP3 inflammasome activation is still unclear. Here, we show that CGRP negatively regulates the antibacterial process of host cells. CGRP prevents NLRP3 inflammasome activation and reduces mature IL-1β secretion. Following NLRP3 inflammasome stimulation that triggers endosome leakage, CGRP internalized to endosomal compartments is released into the cell cytosol. Cytosolic CGRP binds directly to NLRP3 and dismantles the NLRP3-NEK7 complex, which is crucial for NLRP3 inflammasome activation. CGRP administration exacerbates bacterial infection, while the treatment with a CGRP antagonist has the opposite effect. Our study uncovers a unique role of CGRP in inhibiting inflammasome activation during infections, which might shed new light on antibacterial therapies in the future.

关 键 词：NEUROPEPTIDE CGRP NLRP3 INFLAMMASOME SUPPRESSOR 

分 类 号：R563[医药卫生—呼吸系统]