Function and Regulation of Noncanonical Caspase-4/5/11 Inflammasome.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Sampsa MatikainenWojciech Cypryk

Abstract

Inflammasomes are multiprotein complexes of the innate immune system that orchestrate development of inflammation by activating the secretion of proinflammatory cytokines, IL-1β and IL-18. The LPS of Gram-negative bacteria have been shown to activate a novel, noncanonical inflammasome by directly binding in the cytosol to human caspase-4 and mouse caspase-11. Activation of noncanonical inflammasome exerts two major effects: it activates the NLRP3-caspase-1-mediated processing and secretion of IL-1β and IL-18 and induces the inflammatory cell death, pyroptosis, via gasdermin D. This previously unexpected cytosolic LPS sensing of the innate immune system provides critical hints for host response to Gram-negative bacterial infections and development of different inflammatory diseases. However, many of its molecular regulatory mechanisms are yet to be discovered. In this review, we provide comprehensive analysis of current understanding of intracellular LPS detection and pyroptosis via noncanonical inflammasome and discuss the recently proposed mechanisms of its function and regulation.

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Citations

Sep 25, 2020·The Journal of Cell Biology·Sampsa MatikainenWojciech Cypryk
Sep 16, 2020·Cell Death and Differentiation·Andrea PoelzlBirgit Strobl
Sep 4, 2020·Journal of Neuroinflammation·Vaidya GovindarajanRobert W Keane
Feb 23, 2021·Frontiers in Pharmacology·Bohao LiuQing Geng
May 5, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bruno Jennings-AlmeidaAna Carolina Oliveira
Jul 25, 2021·International Journal of Molecular Sciences·Young-Su Yi
Jul 9, 2021·Apoptosis : an International Journal on Programmed Cell Death·Xiaofeng DaiJianying Zhang
Nov 15, 2020·Molecular Aspects of Medicine·Kevin P DownsChristian Stehlik
Jan 23, 2022·Apoptosis : an International Journal on Programmed Cell Death·Ying HuangGuo Wang

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