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Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis
Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis
- Source :
- J Innate Immun, Journal of Innate Immunity, Pp 1-12 (2020)
- Publication Year :
- 2020
- Publisher :
- S. Karger AG, 2020.
-
Abstract
- Double-stranded RNA dependent kinase R (PKR) is originally identified as an intracellular sensor of viral infection, but its role in bacterial infection remains largely unknown. Here we report that PKR was an important regulator of antibacterial immunity in sepsis. Genetic deletion of PKR or pharmacological inhibition of its kinase activity markedly increased bacterial loads, organ injury, and mortality in polymicrobial infection induced by cecal ligation and puncture (CLP). In contrast, PKR deficiency or inhibition did not affect bacterial loads, organ injury, or mortality when mice were systemically challenged with Escherichia coli, an abundant microbe in the gastrointestinal tract. PKR deficiency or inhibition markedly decreased the release of interleukin (IL)-1β after CLP. Defect in IL-1 signaling phenocopied PKR deficiency or inhibition in CLP-induced bacterial sepsis. Taken together, these findings identified a critical role of the PKR signaling pathway in antibacterial immunity.
- Subjects :
- lcsh:Internal medicine
Indoles
viruses
bacterial sepsis
Interleukin-1beta
lcsh:Medicine
Biology
environment and public health
Microbiology
Sepsis
Mice
eIF-2 Kinase
Immunity
Escherichia coli
medicine
Animals
Humans
Immunology and Allergy
Kinase activity
lcsh:RC31-1245
Cecum
Cells, Cultured
Escherichia coli Infections
RNA, Double-Stranded
Mice, Knockout
Kinase
lcsh:R
virus diseases
RNA
Interleukin
biochemical phenomena, metabolism, and nutrition
medicine.disease
Protein kinase R
Immunity, Innate
Mice, Inbred C57BL
enzymes and coenzymes (carbohydrates)
Disease Models, Animal
Thiazoles
double-stranded rna dependent kinase r
Macrophages, Peritoneal
interleukin-1
Intracellular
Signal Transduction
Research Article
Subjects
Details
- ISSN :
- 16628128 and 1662811X
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Journal of Innate Immunity
- Accession number :
- edsair.doi.dedup.....f76738c836258ddf9da6e38c86425bce
- Full Text :
- https://doi.org/10.1159/000507932