期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.752482
关键词
speck; NLRP3; inflammasome; caspase-1; colchicine; IL-1 beta; nigericin; H2O2
类别
资金
- NIH [R01AI072259, P01AI056320, R03AI146596]
The NLRP3:ASC speck is not synonymous with the NLRP3 inflammasome, but is a dynamic structure that can amplify the NLRP3 response to weak stimuli.
Although considered the ternary inflammasome structure, whether the singular, perinuclear NLRP3:ASC speck is synonymous with the NLRP3 inflammasome is unclear. Herein, we report that the NLRP3:ASC speck is not required for nigericin-induced inflammasome activation but facilitates and maximizes IL-1 beta processing. Furthermore, the NLRP3 agonists H2O2 and MSU elicited IL-1 beta maturation without inducing specks. Notably, caspase-1 activity is spatially distinct from the speck, occurring at multiple cytoplasmic sites. Additionally, caspase-1 activity negatively regulates speck frequency and speck size, while speck numbers and IL-1 beta processing are negatively correlated, cyclical and can be uncoupled by NLRP3 mutations or inhibiting microtubule polymerization. Finally, when specks are present, caspase-1 is likely activated after leaving the speck structure. Thus, the speck is not the NLRP3 inflammasome itself, but is instead a dynamic structure which may amplify the NLRP3 response to weak stimuli by facilitating the formation and release of small NLRP3:ASC complexes which in turn activate caspase-1.
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