The Gasdermin-D pore acts as a conduit for IL-1β secretion in mice.

Details

Serval ID
serval:BIB_F4DB5E21C5FE
Type
Article: article from journal or magazin.
Collection
Publications
Title
The Gasdermin-D pore acts as a conduit for IL-1β secretion in mice.
Journal
European Journal of Immunology
Author(s)
Heilig R., Dick M.S., Sborgi L., Meunier E., Hiller S., Broz P.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
48
Number
4
Pages
584-592
Language
english
Abstract
The pro-inflammatory cytokine IL-1β is well known for its role in host defense and the initiation of potent inflammatory responses. It is processed from its inactive pro-form by the inflammatory caspase-1 into its mature bioactive form, which is then released from the cell via an unconventional secretion mechanism. Recently, gasdermin-D has been identified as a new target of caspase-1. After proteolytical cleavage of gasdermin-D, the N-terminal fragment induces pyroptosis, a lytic cell death, by forming large permeability pores in the plasma membrane. Here we show using the murine system that gasdermin-D is required for IL-1β secretion by macrophages, dendritic cells and partially in neutrophils, and that secretion is a cell-lysis-independent event. Liposome transport assays in vitro further demonstrate that gasdermin-D pores are large enough to allow the direct release of IL-1β. Moreover, IL-18 and other small soluble cytosolic proteins can also be released in a lysis-independent but gasdermin-D-dependent mode, suggesting that the gasdermin-D pores allow passive the release of cytosolic proteins in a size-dependent manner.
Keywords
Immunology, Immunology and Allergy, Gasdermin-D pore, inflammasome, interleukin-1β, pyroptosis, unconventional protein secretion, Inflammasome, Interleukin-1β, Pyroptosis, Unconventional protein secretion
Pubmed
Web of science
Create date
26/12/2017 12:58
Last modification date
20/08/2019 17:21
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