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病毒感染后肥大细胞中维甲酸诱导基因-I 样受体的表达和功能特征。

Expression and functional characterization of retinoic acid-inducible gene-I-like receptors of mast cells in response to viral infection.

机构信息

Department of Infection Control Science, Juntendo University School of Medicine, Tokyo, Japan.

出版信息

J Innate Immun. 2013;5(2):163-73. doi: 10.1159/000343895. Epub 2012 Nov 21.

Abstract

To investigate the precise mechanisms of virus recognition by mast cells, the expression and functional characteristics of virus recognition receptors that lead to mast cell activation were investigated. Our results suggest that mast cells are partly responsible for the early in vivo production of antiviral cytokines and chemokines upon vesicular stomatitis virus (VSV) infection. Analysis of the expression of double-stranded RNA (dsRNA) recognition receptors in murine bone marrow-derived mast cells (BMMCs) revealed that BMMCs express melanoma differentiation-associated gene 5 (MDA5), protein kinase RNA-activated, retinoic acid-inducible gene-I (RIG-I) and Toll-like receptor 3. The expression levels of these receptors were found to increase upon stimulation of mast cells with VSV as well as synthetic dsRNA: polyinosinic-polycytidylic acid. Moreover, small interfering RNA analysis to identify the receptors responsible for mast cell activation by VSV revealed that both RIG-I and MDA5 were involved in cytokine production but not in the degranulation of mast cells. Our findings suggest that mast cells produce cytokines and chemokines in the early infection stage after recognizing viruses via RIG-I and MDA5, and may contribute to antiviral responses. These data provide additional novel information that improves our understanding of antiviral innate responses that involve mast cells.

摘要

为了探究肥大细胞识别病毒的精确机制,研究了导致肥大细胞活化的病毒识别受体的表达和功能特征。我们的结果表明,肥大细胞在水泡性口炎病毒(VSV)感染后,部分负责体内早期产生抗病毒细胞因子和趋化因子。对鼠骨髓来源的肥大细胞(BMMCs)中双链 RNA(dsRNA)识别受体的表达分析表明,BMMCs 表达黑色素瘤分化相关基因 5(MDA5)、蛋白激酶 RNA 激活的、视黄酸诱导基因-I(RIG-I)和 Toll 样受体 3。发现这些受体的表达水平在肥大细胞受到 VSV 以及合成 dsRNA:聚肌苷酸-聚胞苷酸刺激时增加。此外,通过小干扰 RNA 分析鉴定参与 VSV 激活肥大细胞的受体表明,RIG-I 和 MDA5 均参与细胞因子的产生,但不参与肥大细胞的脱颗粒。我们的研究结果表明,肥大细胞通过 RIG-I 和 MDA5 在病毒感染的早期阶段产生细胞因子和趋化因子,可能有助于抗病毒反应。这些数据提供了额外的新信息,有助于我们理解涉及肥大细胞的抗病毒先天反应。

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