title: Novel perspectives on non-canonical inflammasome activation.
abstract: Inflammasomes are cytosolic multi-protein complexes that regulate the secretion of the proinflammatory cytokines, IL-1β and IL-18, and induce pyroptosis, an inflammatory form of cell death. The NLRP3 inflammasome is the most well-characterized member of this family and functions by sensing intracellular pathogen- and damage-associated molecular patterns and activating caspase-1, which processes the biologically inactive IL-1β and IL-18 precursors into active cytokines. Recent studies have identified an alternative mechanism of inflammasome activation, termed the non-canonical inflammasome, which is triggered by cytosolic sensing of lipopolysaccharide (LPS) derived from bacteria that have escaped phagolysosomes. This pathway is independent of Toll-like receptor 4 (TLR4), the well-known extracellular receptor for LPS, but instead depends on the inflammatory protease, caspase-11. Although our understanding of caspase-11 activation is still in its infancy, it appears to be an essential mediator of septic shock and attenuates intestinal inflammation. In this review, we bring together the latest data on the roles of caspase-11 and the mechanisms underlying caspase-11-mediated activation of the non-canonical inflammasome, and consider the implications of this pathway on TLR4-independent immune responses to LPS.
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Singapore; Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Catherine Emma
authors.initials: CE
authors.lastname: Diamond
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Singapore.
authors.forename: Hanif Javanmard
authors.initials: HJ
authors.lastname: Khameneh
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: David
authors.initials: D
authors.lastname: Brough
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Singapore.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mortellaro
keywords: IL-18; IL-1β; LPS; NLRP3; caspase-1; caspase-11