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人肥大细胞和上皮细胞对甲型流感病毒暴露后的反应。

Responses of human mast cells and epithelial cells following exposure to influenza A virus.

机构信息

Alberta Respiratory Centre, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Alberta Respiratory Centre, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

出版信息

Antiviral Res. 2019 Nov;171:104566. doi: 10.1016/j.antiviral.2019.104566. Epub 2019 Jul 23.

Abstract

As a part of innate immune defense, the role of mast cells during viral replication has been incompletely understood. In this study, we characterized and compared the responses of the human mast cell line, LAD2, and human lung epithelial cell line, Calu-3, against three influenza A virus strains; A/PR/8/34 (H1N1), A/WS/33 (H1N1) and A/HK/8/68 (H3N2). We found that there were strain-dependent mast cell responses, and different profiles of cytokine, chemokine and antiviral gene expression between the two cell types. All three strains did not induce histamine or β-hexosaminidase release in LAD2. A/HK/8/68 induced release of prostaglandin D2 in LAD2, whereas A/PR/8/34 and A/WS/33 did not. We found that, among those examined, only CCL4 (by A/PR/8/34) was statistically significantly released from LAD2 cells. Furthermore, there was increased mRNA expression of viral recognition receptors (RIG-I and MDA5) and antiviral protein, viperin, but levels and kinetics of the expression were different among the cell types, as well as by the strains examined. Our findings highlight the variability in innate response to different strains of influenza A virus in two human cell types, indicating that further investigation is needed to understand better the role of mast cells and epithelial cells in innate immunity against influenza A viruses.

摘要

作为先天免疫防御的一部分,肥大细胞在病毒复制过程中的作用尚未完全理解。在这项研究中,我们对人肥大细胞系 LAD2 和人肺上皮细胞系 Calu-3 针对三种流感 A 病毒株(A/PR/8/34[H1N1]、A/WS/33[H1N1]和 A/HK/8/68[H3N2])的反应进行了表征和比较。我们发现存在依赖于病毒株的肥大细胞反应,并且两种细胞类型之间的细胞因子、趋化因子和抗病毒基因表达存在不同的模式。三种病毒株均未诱导 LAD2 中的组胺或β-己糖胺酶释放。A/HK/8/68 诱导 LAD2 中前列腺素 D2 的释放,而 A/PR/8/34 和 A/WS/33 则没有。我们发现,在所检查的物质中,只有 CCL4(由 A/PR/8/34 诱导)从 LAD2 细胞中被统计学显著释放。此外,病毒识别受体(RIG-I 和 MDA5)和抗病毒蛋白 viperin 的 mRNA 表达增加,但表达的水平和动力学在细胞类型之间以及所检查的病毒株之间存在差异。我们的研究结果突出了两种人细胞类型对不同流感 A 病毒株的先天反应的可变性,表明需要进一步研究以更好地理解肥大细胞和上皮细胞在针对流感 A 病毒的先天免疫中的作用。

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