The Inflammasome Drives GSDMD-Independent Secondary Pyroptosis and IL-1 Release in the Absence of Caspase-1 Protease Activity.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_0FB097000CD4
Type
Article: article from journal or magazin.
Collection
Publications
Title
The Inflammasome Drives GSDMD-Independent Secondary Pyroptosis and IL-1 Release in the Absence of Caspase-1 Protease Activity.
Journal
Cell reports
Author(s)
Schneider K.S., Groß C.J., Dreier R.F., Saller B.S., Mishra R., Gorka O., Heilig R., Meunier E., Dick M.S., Ćiković T., Sodenkamp J., Médard G., Naumann R., Ruland J., Kuster B., Broz P., Groß O.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
26/12/2017
Peer-reviewed
Oui
Volume
21
Number
13
Pages
3846-3859
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Inflammasomes activate the protease caspase-1, which cleaves interleukin-1β and interleukin-18 to generate the mature cytokines and controls their secretion and a form of inflammatory cell death called pyroptosis. By generating mice expressing enzymatically inactive caspase-1 <sup>C284A</sup> , we provide genetic evidence that caspase-1 protease activity is required for canonical IL-1 secretion, pyroptosis, and inflammasome-mediated immunity. In caspase-1-deficient cells, caspase-8 can be activated at the inflammasome. Using mice either lacking the pyroptosis effector gasdermin D (GSDMD) or expressing caspase-1 <sup>C284A</sup> , we found that GSDMD-dependent pyroptosis prevented caspase-8 activation at the inflammasome. In the absence of GSDMD-dependent pyroptosis, the inflammasome engaged a delayed, alternative form of lytic cell death that was accompanied by the release of large amounts of mature IL-1 and contributed to host protection. Features of this cell death modality distinguished it from apoptosis, suggesting it may represent a distinct form of pro-inflammatory regulated necrosis.
Keywords
Animals, Apoptosis Regulatory Proteins/metabolism, Caspase 1/metabolism, Caspase 8/metabolism, Caspase Inhibitors/pharmacology, Enzyme Activation/drug effects, Francisella/physiology, Immunity, Innate, Inflammasomes/metabolism, Interleukin-1/metabolism, Interleukin-1beta/metabolism, Mice, Inbred C57BL, Pyroptosis/drug effects, ASC, IL-1, caspase-1, caspase-8, gasdermin, inflammasome, pyroptosis, regulated necrosis
Pubmed
Web of science
Open Access
Yes
Create date
15/01/2018 18:43
Last modification date
20/08/2019 13:36
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