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

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外文摘要：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.

外文关键词：

NeuropeptideCGRPNLRP3InflammasomeSuppressor

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

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作者单位：

Department of Immunology,School of Basic Medical Sciences,Peking University,100191 Beijing,China

NHC Key Laboratory of Medical Immunology,Peking University,100191 Beijing,China

Key Laboratory of Molecular Immunology,Chinese Academy of Medical Sciences,100191 Beijing,China

CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,100101 Beijing,China

Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,Hubei 430071,China

Department of Anesthesiology,Peking University Third Hospital,100191 Beijing,China

Department of Sports Medicine,Peking University Third Hospital,100191 Beijing,China

Beijing Key Laboratory of Sports Injuries,Institute of Sports Medicine of Peking University,100191 Beijing,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaBeijing Natural Science FoundationNational Key R&D Program of ChinaNational Key R&D Program of ChinaStrategic Priority Research Programs of the Chinese Academy of SciencesKey Research Program of Frontier Sciences of Chinese Academy of SciencesCAS Project for Young Scientists in Basic ResearchFok Ying Tung Education FoundationYouth Innovation Promotion Association of CAS

项目编号：

81922031822717909216911372120672019YFA01118002022YFC2302900XDB29020000ZDBS-LY-SM025YSBR-010

出版年：

2023

DOI：

10.1038/s41423-022-00968-w

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(3)

参考文献量45