Title |
Noncanonical inflammasome signaling elicits gasdermin D–dependent neutrophil extracellular traps
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Published in |
Science Immunology, August 2018
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DOI | 10.1126/sciimmunol.aar6676 |
Pubmed ID | |
Authors |
Kaiwen W Chen, Mercedes Monteleone, Dave Boucher, Gabriel Sollberger, Divya Ramnath, Nicholas D Condon, Jessica B von Pein, Petr Broz, Matthew J Sweet, Kate Schroder |
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-/- and Gsdmd -/- mice. Our studies reveal that neutrophils use an inflammasome- and GSDMD-dependent mechanism to activate NETosis as a defense response against cytosolic bacteria. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Australia | 14 | 19% |
United Kingdom | 13 | 18% |
United States | 13 | 18% |
Singapore | 2 | 3% |
Canada | 2 | 3% |
Italy | 1 | 1% |
Spain | 1 | 1% |
Algeria | 1 | 1% |
Ireland | 1 | 1% |
Other | 5 | 7% |
Unknown | 19 | 26% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 38 | 53% |
Scientists | 31 | 43% |
Science communicators (journalists, bloggers, editors) | 2 | 3% |
Practitioners (doctors, other healthcare professionals) | 1 | 1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 333 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 63 | 19% |
Researcher | 52 | 16% |
Student > Master | 44 | 13% |
Student > Bachelor | 22 | 7% |
Student > Doctoral Student | 17 | 5% |
Other | 51 | 15% |
Unknown | 84 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 80 | 24% |
Biochemistry, Genetics and Molecular Biology | 63 | 19% |
Agricultural and Biological Sciences | 41 | 12% |
Medicine and Dentistry | 29 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 2% |
Other | 23 | 7% |
Unknown | 91 | 27% |