STING recruits NLRP3 to the ER and deubiquitinates NLRP3 to activate the inflammasome
Muhammad Adnan Shereen,
Posted 24 Jun 2019
bioRxiv DOI: 10.1101/681338
Posted 24 Jun 2019
One of the fundamental reactions of the innate immune responses to pathogen infection is the release of pro-inflammatory cytokines, including IL-1β, processed by the NLRP3 inflammasome. STING is essential for innate immune responses and inflammasome activation. Here we reveal a distinct mechanism by which STING regulates the NLRP3 inflammasome activation, IL-1β secretion, and inflammatory responses in human cell lines, mice primary cells, and mice. Interestingly, upon HSV-1 infection and cytosolic DNA stimulation, STING binds to NLRP3 and promotes the inflammasome activation through two approaches. First, STING recruits NLRP3 and promotes NLRP3 translocation to the endoplasmic reticulum, thereby facilitating the inflammasome formation. Second, STING interacts with NLRP3 and removes K48- and K63-linked polyubiquitination of NLRP3, thereby promoting the inflammasome activation. Collectively, we demonstrate that the cGAS-STING-NLRP3 signaling is essential for host defense against DNA virus infection.
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