Back to Search
Start Over
Taking the STING Out of Sepsis?
- Source :
- Cell Host Microbe
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- The discovery of TMEM173/STING-dependent innate immunity has recently provided guidance for the prevention and management of inflammatory disorders. Here, we show that myeloid TMEM173 occupies an essential role in regulating coagulation in bacterial infections through a mechanism independent of type I interferon response. Mechanistically, TMEM173 binding to ITPR1 controls calcium release from the endoplasmic reticulum in macrophages and monocytes. The TMEM173-dependent increase in cytosolic calcium drives Gasdermin D (GSDMD) cleavage and activation, which triggers the release of F3, the key initiator of blood coagulation. Genetic or pharmacological inhibition of the TMEM173-GSDMD-F3 pathway blocks systemic coagulation and improves animal survival in three models of sepsis (cecal ligation and puncture or bacteremia with Escherichia coli or Streptococcus pneumoniae infection). The upregulation of the TMEM173 pathway correlates with the severity of disseminated intravascular coagulation and mortality in patients with sepsis. Thus, TMEM173 is a key regulator of blood clotting during lethal bacterial infections.
- Subjects :
- 0303 health sciences
Pathogen detection
Macrophages
Membrane Proteins
Gasdermin D
Biology
medicine.disease
Microbiology
Article
eye diseases
Sepsis
Disease Models, Animal
Mice
03 medical and health sciences
Sting
0302 clinical medicine
Virology
Immunology
medicine
Animals
Parasitology
030217 neurology & neurosurgery
030304 developmental biology
Subjects
Details
- ISSN :
- 19313128
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Cell Host & Microbe
- Accession number :
- edsair.doi.dedup.....5bcdcb23eb5564c782818a2a1b8ccd2c