Caspase-1 autoproteolysis is differentially required for NLRP1b and NLRP3 inflammasome function

In the context of the nucleotide-binding domain and leucine rich repeat pyrin containing 1b (NLRP1b) inflammasome activation by anthrax lethal toxin, we reveal a new role for full-length caspase-1. We directly demonstrate that the caspase-1 45-kDa zymogen is able to process pro–IL-1β and to induce pyroptosis, and that apoptosis-associated speck-like protein containing a CARD is dispensable for the activity of the NLRP1b inflammasome. This is in contrast to the NLRP3 inflammasome activity, which is inhibited in the absence of caspase-1 autoproteolyis. Our data, which highlight differential requirements for caspase-1 autoproteolysis in NLRP1b and NLRP3 inflammasome function, may have implications for pathogen recognition and response.