Inflammasome Activation Triggers Blood Clotting and Host Death through Pyroptosis.
Animals
Bacterial Infections
/ complications
Biomarkers
Blood Coagulation
Caspases
/ metabolism
Cell-Derived Microparticles
/ immunology
Disease Models, Animal
Humans
Inflammasomes
/ metabolism
Lipopolysaccharides
/ immunology
Macrophages
/ immunology
Mice
Monocytes
/ immunology
Pyroptosis
Signal Transduction
Thromboplastin
/ metabolism
Thrombosis
/ blood
DIC
GSDMD
LPS
caspase
coagulation
inflammasome
macrophage
pyroptosis
sepsis
tissue factor
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
18 06 2019
18 06 2019
Historique:
received:
26
10
2018
revised:
04
02
2019
accepted:
11
04
2019
pubmed:
12
5
2019
medline:
2
11
2019
entrez:
12
5
2019
Statut:
ppublish
Résumé
Inflammasome activation and subsequent pyroptosis are critical defense mechanisms against microbes. However, overactivation of inflammasome leads to death of the host. Although recent studies have uncovered the mechanism of pyroptosis following inflammasome activation, how pyroptotic cell death drives pathogenesis, eventually leading to death of the host, is unknown. Here, we identified inflammasome activation as a trigger for blood clotting through pyroptosis. We have shown that canonical inflammasome activation by the conserved type III secretion system (T3SS) rod proteins from Gram-negative bacteria or noncanonical inflammasome activation by lipopolysaccharide (LPS) induced systemic blood clotting and massive thrombosis in tissues. Following inflammasome activation, pyroptotic macrophages released tissue factor (TF), an essential initiator of coagulation cascades. Genetic or pharmacological inhibition of TF abolishes inflammasome-mediated blood clotting and protects against death. Our data reveal that blood clotting is the major cause of host death following inflammasome activation and demonstrate that inflammasome bridges inflammation with thrombosis.
Identifiants
pubmed: 31076358
pii: S1074-7613(19)30183-9
doi: 10.1016/j.immuni.2019.04.003
pmc: PMC6791531
mid: NIHMS1528326
pii:
doi:
Substances chimiques
Biomarkers
0
Inflammasomes
0
Lipopolysaccharides
0
Thromboplastin
9035-58-9
Caspases
EC 3.4.22.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1401-1411.e4Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM121796
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL123927
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI103717
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI137020
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142640
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM132443
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI142063
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM085231
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM127211
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103527
Pays : United States
Organisme : NHLBI NIH HHS
ID : K99 HL145117
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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