RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway

被引：275

作者：

Wang, Xiaqiong ^{[1
,2
,3
]}

Jiang, Wei ^{[1
,2
,3
]}

Yan, Yiqing ^{[1
,2
,3
]}

Gong, Tao ^{[1
,2
,3
]}

Han, Jiahuai ^{[4
]}

Tian, Zhigang ^{[1
,2
,3
,5
]}

Zhou, Rongbin ^{[1
,2
,3
,5
]}

机构：

[1] Univ Sci & Technol China, Sch Life Sci, Inst Immunol, Hefei 230026, Peoples R China

[2] Univ Sci & Technol China, Sch Life Sci, CAS Key Lab Innate Immun & Chron Dis, Hefei 230026, Peoples R China

[3] Univ Sci & Technol China, Med Ctr, Hefei 230026, Peoples R China

[4] Xiamen Univ, Innovat Ctr Cell Biol, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen, Fujian, Peoples R China

[5] Innovat Ctr Cell Biol, Hefei Natl Lab Phys Sci Microscale, Hefei, Peoples R China

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 12期

基金：

中国国家自然科学基金;

关键词：

INFLUENZA-VIRUS; CELL-DEATH; CASPASE-8; KINASE; RIP3; APOPTOSIS; NECROSIS; IMMUNITY; DRP1; DNA;

D O I：

10.1038/ni.3015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The NLRP3 inflammasome functions as a crucial component of the innate immune system in recognizing viral infection, but the mechanism by which viruses activate this inflammasome remains unclear. Here we found that inhibition of the serine-threonine kinases RIP1 (RIPK1) or RIP3 (RIPK3) suppressed RNA virus-induced activation of the NLRP3 inflammasome. Infection with an RNA virus initiated assembly of the RIP1-RIP3 complex, which promoted activation of the GTPase DRP1 and its translocation to mitochondria to drive mitochondrial damage and activation of the NLRP3 inflammasome. Notably, the RIP1-RIP3 complex drove the NLRP3 inflammasome independently of MLKL, an essential downstream effector of RIP1-RIP3-dependent necrosis. Together our results reveal a specific role for the RIP1-RIP3-DRP1 pathway in RNA virus-induced activation of the NLRP3 inflammasome and establish a direct link between inflammation and cell-death signaling pathways.

引用

页码：1126 / 1133

页数：8

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