Journal
NATURE IMMUNOLOGY
Volume 15, Issue 12, Pages 1126-1133Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3015
Keywords
-
Categories
Funding
- National Basic Research Program of China [2014CB910800]
- National Natural Science Foundation of China [81330078, 81222040]
- Doctoral Fund of the Ministry of Education of China [20123402120001, 20123402110010]
- One Hundred Person Project
- Fundamental Research Funds for the Central Universities
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available