Figure 3.

Activation signals of inflammasomes. Signal 1 is provided by ligands of other pattern recognition receptors like TLR4, which, upon binding to exogenous pathogen-associated molecular patterns like LPSs, activates the downstream NFκB signaling pathway. NFκB translocates to the nucleus and induces expression of NLRP3 as well as other proinflammatory cytokines. Signal 2 includes organelle dysfunction (e.g., loss of plasma membrane integrity, lysosome rupture, mitochondrial dysfunction, ROS production, or autophagy induced by endoplasmic reticulum stress), invasion of microbial products (e.g., microbial protein, DNA), and perturbed homeostatic set points of cellular processes (e.g., aberrations in metabolites or influx of ions). Once assembled, the inflammasomes activate caspase-1, which subsequently cleaves the proinflammatory IL-1 family of cytokines into their bioactive forms, leading to pyroptosis. ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; ER, endoplasmic reticulum; NLRP3, NOD-like receptor protein 3; ROS, reactive oxygen species.