Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps.

Details

Serval ID
serval:BIB_96CCEAA6A9DE
Type
Article: article from journal or magazin.
Collection
Publications
Title
Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps.
Journal
Science immunology
Author(s)
Chen K.W., Monteleone M., Boucher D., Sollberger G., Ramnath D., Condon N.D., von Pein J.B., Broz P., Sweet M.J., Schroder K.
ISSN
2470-9468 (Electronic)
ISSN-L
2470-9468
Publication state
Published
Issued date
24/08/2018
Peer-reviewed
Oui
Volume
3
Number
26
Pages
eaar6676
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Neutrophil extrusion of neutrophil extracellular traps (NETs) and concomitant cell death (NETosis) provides host defense against extracellular pathogens, whereas macrophage death by pyroptosis enables defense against intracellular pathogens. We report the unexpected discovery that gasdermin D (GSDMD) connects these cell death modalities. We show that neutrophil exposure to cytosolic lipopolysaccharide or cytosolic Gram-negative bacteria (Salmonella ΔsifA and Citrobacter rodentium) activates noncanonical (caspase-4/11) inflammasome signaling and triggers GSDMD-dependent neutrophil death. GSDMD-dependent death induces neutrophils to extrude antimicrobial NETs. Caspase-11 and GSDMD are required for neutrophil plasma membrane rupture during the final stage of NET extrusion. Unexpectedly, caspase-11 and GSDMD are also required for early features of NETosis, including nuclear delobulation and DNA expansion; this is mediated by the coordinate actions of caspase-11 and GSDMD in mediating nuclear membrane permeabilization and histone degradation. In vivo application of deoxyribonuclease I to dissolve NETs during murine Salmonella ΔsifA challenge increases bacterial burden in wild-type but not in Casp11 <sup>-/-</sup> and Gsdmd  <sup>-/-</sup> mice. Our studies reveal that neutrophils use an inflammasome- and GSDMD-dependent mechanism to activate NETosis as a defense response against cytosolic bacteria.
Keywords
Animals, Apoptosis Regulatory Proteins/genetics, Apoptosis Regulatory Proteins/immunology, Caspases/immunology, Cell Death, Citrobacter rodentium, Cytosol/immunology, Cytosol/microbiology, Extracellular Traps/immunology, Female, Humans, Inflammasomes/immunology, Lipopolysaccharides, Macrophages/immunology, Male, Mice, Inbred C57BL, Mice, Knockout, Neutrophils/immunology, Salmonella Infections/immunology, Salmonella enterica
Pubmed
Web of science
Create date
04/09/2018 10:28
Last modification date
20/08/2019 15:58
Usage data