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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

Authors :
Fang Liang
Kai Zhao
Yiting Tang
Qianqian Xue
Yanliang Yang
Xiaoli Zhong
Ran Meng
Lingli Xie
Yanjun Zhong
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.

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