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

Eur J Immunol. 2018 Apr;48(4):584-592. doi: 10.1002/eji.201747404. Epub 2018 Jan 15.


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: Gasdermin-D pore; Inflammasome; Interleukin-1β; Pyroptosis; Unconventional protein secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Caspase 1 / genetics
  • Caspase 1 / metabolism*
  • Cells, Cultured
  • Dendritic Cells / metabolism
  • Interleukin-1beta / metabolism*
  • Intracellular Signaling Peptides and Proteins
  • Liposomes / metabolism*
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Phosphate-Binding Proteins
  • Protein Transport / physiology
  • Pyroptosis / physiology


  • Apoptosis Regulatory Proteins
  • Gsdmd protein, mouse
  • IL1B protein, mouse
  • Interleukin-1beta
  • Intracellular Signaling Peptides and Proteins
  • Liposomes
  • Phosphate-Binding Proteins
  • Casp1 protein, mouse
  • Caspase 1