Fig. 3
From: The gasdermin family: emerging therapeutic targets in diseases
The activation mechanisms of canonical inflammasomes. The convergence of canonical inflammasome components is a crucial step in triggering pyroptosis. A diverse array of PAMPs and DAMPs, such as toxins and nucleic acids, serves as a trigger for NLRP3 inflammasome priming, leading to the recruitment of ASC and pro-caspase-1. The T3SS initiates NLRC4 inflammasome activation via NAIP, and NLRC4 mediates NLRP3 inflammasome activation by engaging ASC or through direct CARD-CARD domain interactions, which promotes the recruitment of pro-caspase-1 into the assembly complex. Anthrax lethal toxin stimulates the NLRP1 inflammasome, resulting in the activation of pro-caspase-1, which can occur either contingently or independently of ASC recruitment. The AIM2 inflammasome assembles upon detection of dsDNA from host or pathogenic sources. Pyrin inflammasome activation occurs due to bacterial toxins and RhoA-modifying proteins. Both AIM2 and Pyrin engage ASC-mediated signaling to orchestrate the activation of pro-caspase-1. Upon activation, caspase-1 executes its function by cleaving GSDMD and pro-IL-1β/pro-IL-18, thereby facilitating the release of these cytokines via a channel formed by GSDMD-NT
