The NLRP3 inflammasome is dysregulated in XIAP deficiency. (A) BMDMs from 4 different mouse strains were preincubated with CpG ODN, TNF-α, or media as control. XIAP KO cells readily produced IL-1β with a single priming stimulation, but this was reduced in XIAP-NLRP3 double KO cells, clearly implying the role of NLRP3 in XIAP deficiency-mediated inflammasome dysregulation. (B) Similarly, the role of the NLRP3 inflammasome in XIAP deficiency-mediated inflammasome dysregulation was also evident in the presence of nigericin. (C) The addition of a caspase-8 inhibitor further reduced residual IL-1beta activation and secretion when cells were primed with CpG ODN or TNF-α alone or (D) additionally activated with nigericin, acting in an inflammasome-independent manner. Symbols used: n.s for not significant, * for p≤0.05, and ** for p≤0.01.