LAUSR

Immune antigen-presenting cells and skin and mucosal epithelia vigorously respond to invasive microbial infection. When NOD-like receptors (NLRs) or AIM2-like receptors (ALRs) in the immune cell cytosol sense microbial products, they assemble the canonical inflammasome, which activates caspase-1 (initially called ICE).1 Caspases-4/5 in humans and caspase-11 in mice, expressed by immune cells and epithelial barrier cells, directly sense cytosolic lipopolysaccharide (LPS) from Gram− bacterial cell walls.2 These caspases are directly activated in an LPS–inflammatory caspase complex (the noncanonical inflammasome).3, 4 Inflammatory caspase activation causes a ‘fiery’ death, pyroptosis, that is morphologically and functionally distinct from apoptosis or necroptosis.5, 6 Caspase-1, but not other inflammatory caspases, also process and cause release of inflammatory cytokines (including IL-1β, IL-18) that cause fever. Triggering the noncanonical inflammasome indirectly activates the canonical inflammasome.3