A bacterial phospholipid phosphatase inhibits host pyroptosis by hijacking ubiquitin

被引：109

作者：

Chai, Qiyao ^{[1
]}

Yu, Shanshan ^{[2
]}

Zhong, Yanzhao ^{[1
,3
]}

Lu, Zhe ^{[1
,3
]}

Qiu, Changgen ^{[1
,3
]}

Yu, Yang ^{[1
,3
]}

Zhang, Xinwen ^{[1
,3
]}

Zhang, Yong ^{[1
]}

Lei, Zehui ^{[1
,3
]}

Qiang, Lihua ^{[1
,3
]}

Li, Bing-Xi ^{[1
]}

Pang, Yu ^{[2
]}

Qiu, Xiao-Bo ^{[1
,4
,5
]}

Wang, Jing ^{[1
]}

Liu, Cui Hua ^{[1
,3
]}

机构：

[1] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China

[2] Capital Med Univ, Beijing TB & Thorac Tumor Res Inst, Beijing Chest Hosp, Beijing 101149, Peoples R China

[3] Univ Chinese Acad Sci, Savaid Med Sch, Beijing 101408, Peoples R China

[4] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 211198, Jiangsu, Peoples R China

[5] Beijing Normal Univ, Coll Life Sci, Minist Educ, Key Lab Cell Proliferat & Regulat Biol, Beijing 100875, Peoples R China

来源：

SCIENCE | 2022年 / 378卷 / 6616期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

GASDERMIN-D; TUBERCULOSIS; MULTIPLE; RNA; MECHANISM; PORE;

D O I：

10.1126/science.abq0132

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The inflammasome-mediated cleavage of gasdermin D (GSDMD) causes pyroptosis and inflammatory cytokine release to control pathogen infection, but how pathogens evade this immune response remains largely unexplored. Here we identify the known protein phosphatase PtpB from Mycobacterium tuberculosis as a phospholipid phosphatase inhibiting the host inflammasome-pyroptosis pathway. Mechanistically, PtpB dephosphorylated phosphatidylinositol-4-monophosphate and phosphatidylinositol-(4,5)-bisphosphate in host cell membrane, thus disrupting the membrane localization of the cleaved GSDMD to inhibit cytokine release and pyroptosis of macrophages. Notably, this phosphatase activity requires PtpB binding to ubiquitin. Disrupting phospholipid phosphatase activity or the ubiquitin-interacting motif of PtpB enhanced host GSDMD-dependent immune responses and reduced intracellular pathogen survival. Thus, pathogens inhibit pyroptosis and counteract host immunity by altering host membrane composition.

引用

页码：153 / +

页数：16

共 53 条

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