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

Heilig, Rosalie and Dick, Mathias S. and Sborgi, Lorenzo and Meunier, Etienne and Hiller, Sebastian and Broz, Petr. (2018) The Gasdermin-D pore acts as a conduit for IL-1β secretion in mice. European journal of immunology, 48 (4). pp. 584-592.

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Official URL: https://edoc.unibas.ch/59182/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Infection Biology (Broz)
05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Hiller)
UniBasel Contributors:Hiller Odermatt, Sebastian and Broz, Petr
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Jul 2018 15:51
Deposited On:05 Jul 2018 15:51

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