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.
J Innate Immun

中文翻译：

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双链 RNA 依赖性激酶 R 调节脓毒症中的抗菌免疫

双链 RNA 依赖性激酶 R (PKR) 最初被确定为病毒感染的细胞内传感器，但其在细菌感染中的作用仍然未知。在这里我们报告 PKR 是脓毒症抗菌免疫的重要调节剂。PKR 的基因缺失或其激酶活性的药理学抑制显着增加了盲肠结扎和穿刺 (CLP) 诱导的多种微生物感染的细菌负荷、器官损伤和死亡率。相比之下，当小鼠全身受到大肠杆菌攻击时，PKR 缺乏或抑制不会影响细菌负荷、器官损伤或死亡率, 胃肠道中丰富的微生物。PKR 缺乏或抑制显着降低了 CLP 后白细胞介素 (IL)-1β 的释放。IL-1 信号缺陷导致 PKR 缺乏或抑制 CLP 诱导的细菌性败血症。总之，这些发现确定了 PKR 信号通路在抗菌免疫中的关键作用。
J先天免疫