Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis
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 pharmac...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2020-12-01
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| Series: | Journal of Innate Immunity |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/507932 |
| _version_ | 1818960211125207040 |
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| author | Yanliang Yang Lingli Xie Yanjun Zhong Xiaoli Zhong Ran Meng Qianqian Xue Fang Liang Kai Zhao Yiting Tang |
| author_facet | Yanliang Yang Lingli Xie Yanjun Zhong Xiaoli Zhong Ran Meng Qianqian Xue Fang Liang Kai Zhao Yiting Tang |
| author_sort | Yanliang Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T11:53:55Z |
| format | Article |
| id | doaj.art-44893b97e8bf4a97abf2f79d1fabb12e |
| institution | Directory Open Access Journal |
| issn | 1662-811X 1662-8128 |
| language | English |
| last_indexed | 2024-12-20T11:53:55Z |
| publishDate | 2020-12-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj.art-44893b97e8bf4a97abf2f79d1fabb12e2022-12-21T19:41:43ZengKarger PublishersJournal of Innate Immunity1662-811X1662-81282020-12-0111210.1159/000507932507932Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in SepsisYanliang YangLingli XieYanjun ZhongXiaoli ZhongRan MengQianqian XueFang LiangKai ZhaoYiting TangDouble-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.https://www.karger.com/Article/FullText/507932double-stranded rna dependent kinase rbacterial sepsisinterleukin-1 |
| spellingShingle | Yanliang Yang Lingli Xie Yanjun Zhong Xiaoli Zhong Ran Meng Qianqian Xue Fang Liang Kai Zhao Yiting Tang Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis Journal of Innate Immunity double-stranded rna dependent kinase r bacterial sepsis interleukin-1 |
| title | Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis |
| title_full | Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis |
| title_fullStr | Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis |
| title_full_unstemmed | Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis |
| title_short | Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis |
| title_sort | double stranded rna dependent kinase r regulates antibacterial immunity in sepsis |
| topic | double-stranded rna dependent kinase r bacterial sepsis interleukin-1 |
| url | https://www.karger.com/Article/FullText/507932 |
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