FIGURE 23-4 The NLRP3 inflammasome. The NLRP3 inflammasome activates caspase-1 only after receiving two signals. Signal 1 is provided by microbial antigens recognized via Toll-like receptors (TLRs) or by binding of endogenous cytokines such as TNF to the TNF receptor (TNFR). Signal 1 causes the up-regulation of NLRP3 and pro-IL-1β. Signal 2, which activates the NLRP3 inflammasome, can be provided by bacterial pore-forming toxins, by influenza virus M2 protein, by fungal particles via the kinase Syk (as shown for Candida albicans), or by cholera toxin (CT). Cytosolic bacterial DNA can also activate the NLRP3 inflammasome, although the molecular details of this mechanism are not yet understood.