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首页> 外文期刊>Cellular immunology >Protease-activated receptor 4 protects mice from Coxsackievirus B3 and H1N1 influenza A virus infection
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Protease-activated receptor 4 protects mice from Coxsackievirus B3 and H1N1 influenza A virus infection

机译：蛋白酶激活受体4保护小鼠免受Coxsackeivirus B3和H1N1流感的病毒感染

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PAR4 is expressed by a variety of cells, including platelets, cardiac, lung and immune cells. We investigated the contribution of PAR4 to viral infections of the heart and lung. Toll-like receptor (TLR) 3-dependent immune responses were analyzed after co-stimulation of PAR4 in murine bone-marrow derived macrophages, embryonic fibroblasts and embryonic cardiomyocytes. In addition, we analyzed Coxsackievirus B3 (CVB3) or H1N1 influenza A virus (H1N1 IAV) infection of PAR4(-/-) (Delta PAR4) and wild-type (WT) mice. Lastly, we investigated the effect of platelet inhibition on H1N1 IAV infection. In vitro experiments revealed that PAR4 stimulation enhances the expression of TLR3-dependent CXCL10 expression and decreases TLR3-dependent NF kappa B-mediated proinflammatory gene expression. Furthermore, CVB3-infected Delta PAR4 mice exhibited a decreased anti-viral response and increased viral genomes in the heart leading to more pronounced CVB3 myocarditis compared to WT mice. Similarly, H1N1 IAV-infected Delta PAR4 mice had increased immune cell numbers and inflammatory mediators in the lung, and increased mortality compared with infected WT controls. The study showed that PAR4 protects mice from viral infections of the heart and lung.
机译：PAR4由各种细胞表达，包括血小板，心脏，肺和免疫细胞。我们调查了PAR4对心脏和肺病毒感染的贡献。在鼠骨髓衍生的巨噬细胞，胚胎成纤维细胞和胚胎心肌细胞的共同刺激后，分析了依赖于受体（TLR）3依赖性免疫应答。此外，我们分析了Coxsackievirus B3（CVB3）或H1N1流感的病毒（H1N1 IAV）感染PAR4（ - / - ）（Delta PAR4）和野生型（WT）小鼠。最后，我们研究了血小板抑制对H1N1 IAV感染的影响。体外实验表明，PAR4刺激增强了TLR3依赖性CXCL10表达的表达，降低了TLR3依赖性NFκB介导的促炎基因表达。此外，CVB3感染的Delta Par4小鼠表现出降低的抗病毒反应和心脏中的病毒基因组增加，导致与WT小鼠相比更明显的CVB3心肌炎。类似地，H1N1 IAV感染的Delta Par4小鼠在肺中增加免疫细胞数和炎症介质，以及与受感染的WT对照相比的死亡率增加。该研究表明，PAR4保护小鼠免受心脏和肺的病毒感染。

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