title: Alternative inflammasome activation enables IL-1β release from living cells.
abstract: Classical modes of NLRP3 activation entail a priming step that enables its activation (signal 1) and a potassium efflux-dependent activation signal (signal 2) that triggers pyroptosome formation and pyroptosis, a lytic cell death necessary for IL-1β release. Opposing to that, human monocytes engage an alternative NLRP3 inflammasome pathway in response to LPS that proceeds in the absence of signal 2 activation and enables IL-1β secretion without pyroptosis. This specifically relies on Caspase-8 to propagate signaling to NLRP3, leading to inflammasome activation in absence of pyroptosome formation. Here, we summarize the current knowledge about alternative inflammasome activation, discuss potential extensions of this signaling entity beyond LPS-dependent activation, speculate about its role in tissue homeostasis and sterile inflammation and highlight the implications of pyroptosis-independent IL-1β secretion.
authors.affiliation: Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
authors.forename: Moritz M
authors.initials: MM
authors.lastname: Gaidt
authors.affiliation: Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany. Electronic address: hornung@genzentrum.lmu.de.
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
mesh_terms: D000818:Animals; D053181:Caspase 8 / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D027961:Potassium-Hydrogen Antiporters / Q000378:metabolism; D000069292:Pyroptosis; D015398:Signal Transduction
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D027961:Potassium-Hydrogen Antiporters; D053181:Caspase 8