Fig. 4. Inflammasomes and related molecules contribute to the killing and clearance of gastrointestinal pathogens in intestinal cells and immune cells.
a | Inflammasomes mediate host protection against Gram-negative bacteria by inducing the secretion of IL-1β and IL-18 and pyroptosis55,59,84,85,91,92,254,255. NLRP6 and NLRP12 negatively regulate inflammation133,134,256,257. NLRP6 responds to Toll-like receptor (TLR)-induced autophagy in goblet cells and mediates secretion of mucus137. RNA-bound DEAH box protein 9 (DHX9) interacts with NLRP9b, inducing the assembly of an inflammasome complex161. The NLRP6–DHX15 complex binds to viral RNA and induces the production of type I and type III interferons165. b | Intestinal macrophages can discriminate pathogens from commensals85. c | Activation of caspase 1, caspase 8 or caspase 11 leads to cell death, which removes and extrudes the infected enterocyte from the epithelium93,94,104. d | The inflammasome can reduce bacterial load by inhibiting bacterial uptake, which limits macrophage movement and stiffness, and can promote the production of reactive oxygen species (ROS)105. Pyroptotic macrophages liberate either whole bacteria or bacteria entrapped within pore-induced intracellular traps103. These entities are phagocytosed by neutrophils84,106. ASC, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (CARD); dsRNA, double-stranded RNA; EMCV, encephalomyocarditis virus; KC, keratinocyte chemoattractant (also known as CXCL1); MAVS, mitochondrial antiviral-signalling protein; NAIP, neuronal apoptosis inhibitory protein; NF-κB, nuclear factor-κB; NLRC4, nucleotide-binding domain, leucine-rich repeat-containing protein (NLR) family CARD domain-containing protein 4; ssRNA, single-stranded RNA.