Caspase-1 and Gasdermin D Afford the Optimal Targets with Distinct Switching Strategies in NLRP1b Inflammasome-Induced Cell Death.

ABSTRACT: Inflammasomes are essential complexes of innate immune system, which form the first line of host defense against pathogens. Mounting evidence accumulates that inflammasome signaling is highly correlated with coronavirus disease 2019 (COVID-19). However, there remains a significant gap in our understanding of the regulatory mechanism of inflammasome signaling. Combining mathematical modeling with experimental analysis of NLRP1b inflammasome signaling, we found that only the expression levels of caspase-1 and GSDMD have the potential to individually switch cell death modes. Reduction of caspase-1 or GSDMD switches cell death from pyroptosis to apoptosis. Caspase-1 and GSDMD present different thresholds and exert distinct pathway choices in switching death modes. Pyroptosis switches to apopto

SUBMITTER: Li X 

PROVIDER: S-EPMC9343085 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature