cFLIPs regulates alternative NLRP3 inflammasome activation in human monocytes

扫码查看

原文链接

万方数据

外文摘要：The innate immune responses,including inflammasome activation,are paramount for host defense against pathogen infection.In contrast to canonical and noncanonical inflammasome activation,in this study,heat-killed gram-negative bacteria(HK bacteria)were identified as single-step stimulators of the NLRP3 inflammasome in human monocytes,and they caused a moderate amount of IL-1 β to be released from cells.Time course experiments showed that this alternative inflammasome response was finished within a few hours.Further analysis showed that the intrinsically limited NLRP3 inflammasome activation response was due to the negative regulation of caspase-8 by the short isoform of cFLIP(cFLIPs),which was activated by NF-κB.In contrast,overexpressed cFLIPs,but not overexpressed cFLIPL,inhibited the activation of caspase-8 and the release of IL-1 β in response to HK bacteria infection in human monocytes.Furthermore,we demonstrated that TAK1 activity mediated the expression of cFLIPs and was upstream and essential for the caspase-8 cleavage induced by HK bacteria in human monocytes.The functional specificity of cFLIPs and TAK1 revealed unique responses of human monocytes to a noninvasive pathogen,providing novel insights into an alternative regulatory pathway of NLRP3 inflammasome activation.

外文关键词：

cFLIPSgram-negative bacteriaNLRP3 inflammasomehuman monocyte

作者：

Yuhui Gao、Shi Yu、Mengdan Chen、Xun Wang、Lei Pan、Bin Wei、Guangxun Meng

展开 >

作者单位：

School of Life Sciences,Shanghai University,Shanghai 200444,China

The Center for Microbes,Development and Health,CAS Key Laboratory of Molecular Virology &Immunology,University of Chinese Academy of Sciences,Shanghai 200031,China

Department of Basic Research,Guangzhou Laboratory,Guangzhou International Bio-Island,Guangzhou 510005 Guangdong,China

Shanghai Blood Center,Shanghai 200051,China

Pasteurien College,Soochow University,Suzhou 215006 Jiangsu,China

Nanjing Advanced Academy of Life and Health,Nanjing 211135 Jiangsu,China

展开 >

基金：

Natural Science Foundation of ChinaNatural Science Foundation of ChinaNational Key R&D ProgramNational Key R&D ProgramNational Key R&D ProgramStrategic Priority Research ProgramInternational Partnership ProgramChinese Academy of Sciences,Shanghai Municipal Science and Technology Major ProjectResearch Leader ProgramInnovation Capacity Building Project of Jiangsu Province

项目编号：

81830049922692022022YFC23047002022YFC23032002018YFA0507300XDB29030303153831KYSB201900082019SHZDZX0220XD1403900BM2020019

出版年：

2023

DOI：

10.1038/s41423-023-01077-y

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(10)

参考文献量57