Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.653883
Keywords
innate immunity; nod-like receptors; anti-viral; DEAD-box helicase; inflammasome; IL-1; type I interferon
Categories
Funding
- Landesgraduiertenforderung of Baden-Wurttemberg - Science Foundation Ireland
- Irish Health Research Board
Ask authors/readers for more resources
The study reveals that NLRP11 plays a role in regulating type I IFN induction during viral infection and controls NLRP3 inflammasome activation by binding to DDX3X. NLRP11 abolishes IKK epsilon-mediated phosphorylation of DDX3X, leading to reduced type I IFN induction upon viral infection. By interacting with DDX3X through the LRR domain, NLRP11 suppresses NLRP3-mediated inflammasome activation.
Tight regulation of inflammatory cytokine and interferon (IFN) production in innate immunity is pivotal for optimal control of pathogens and avoidance of immunopathology. The human Nod-like receptor (NLR) NLRP11 has been shown to regulate type I IFN and pro-inflammatory cytokine responses. Here, we identified the ATP-dependent RNA helicase DDX3X as a novel binding partner of NLRP11, using co-immunoprecipitation and LC-MS/MS. DDX3X is known to enhance type I IFN responses and NLRP3 inflammasome activation. We demonstrate that NLRP11 can abolish IKK epsilon-mediated phosphorylation of DDX3X, resulting in lower type I IFN induction upon viral infection. These effects were dependent on the LRR domain of NLRP11 that we mapped as the interaction domain for DDX3X. In addition, NLRP11 also suppressed NLRP3-mediated caspase-1 activation in an LRR domain-dependent manner, suggesting that NLRP11 might sequester DDX3X and prevent it from promoting NLRP3-induced inflammasome activation. Taken together, our data revealed DDX3X as a central target of NLRP11, which can mediate the effects of NLRP11 on type I IFN induction as well as NLRP3 inflammasome activation. This expands our knowledge of the molecular mechanisms underlying NLRP11 function in innate immunity and suggests that both NLRP11 and DDX3X might be promising targets for modulation of innate immune responses.
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