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Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling.
- Source :
-
Nature . 10/29/2015, Vol. 526 Issue 7575, p666-671. 6p. 3 Diagrams, 2 Charts, 11 Graphs. - Publication Year :
- 2015
-
Abstract
- Intracellular lipopolysaccharide from Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Burkholderia thailandensis activates mouse caspase-11, causing pyroptotic cell death, interleukin-1β processing, and lethal septic shock. How caspase-11 executes these downstream signalling events is largely unknown. Here we show that gasdermin D is essential for caspase-11-dependent pyroptosis and interleukin-1β maturation. A forward genetic screen with ethyl-N-nitrosourea-mutagenized mice links Gsdmd to the intracellular lipopolysaccharide response. Macrophages from Gsdmd−/− mice generated by gene targeting also exhibit defective pyroptosis and interleukin-1β secretion induced by cytoplasmic lipopolysaccharide or Gram-negative bacteria. In addition, Gsdmd−/− mice are protected from a lethal dose of lipopolysaccharide. Mechanistically, caspase-11 cleaves gasdermin D, and the resulting amino-terminal fragment promotes both pyroptosis and NLRP3-dependent activation of caspase-1 in a cell-intrinsic manner. Our data identify gasdermin D as a critical target of caspase-11 and a key mediator of the host response against Gram-negative bacteria. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 526
- Issue :
- 7575
- Database :
- Academic Search Index
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 110585276
- Full Text :
- https://doi.org/10.1038/nature15541