Alternative inflammasome activation enables IL-1β release from living cells. (February 2017)

• Record Type: Journal Article
• Authors: Gaidt, Moritz M; Hornung, Veit
• Is Part Of: Current opinion in immunology. Volume 44(2017)
• Page Start: 7
• Page End: 13
• Publication Date: 2017-02
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2016.10.007
• Languages: English
• ISSNs: 0952-7915

Abstract

Highlights: Alternative NLRP3 inflammasome activation comprises a distinct signaling entity. Genetic and phenotypic criteria distinguish alternative and classical NLRP3 signaling. This includes absence of pyroptosis and GSDMD-independent IL-1β secretion. 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.