Mumps virus infection disrupts blood-testis barrier through the induction of TNF-alpha in Sertoli cells.
Mumps virus infection disrupts blood-testis barrier through the induction of TNF-alpha in Sertoli cells.
复制标题
腮腺炎病毒感染通过在支持细胞中诱导 TNF-α 来破坏血睾屏障。
DOI：
10.1096/fj.201901089r
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Han Daishu
中科院分区：
文献类型：
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作者：
Wu Han;Jiang Xing;Gao Yunxiao;Liu Weihua;Wang Fei;Gong Maolei;Chen Ran;Yu Xiaoqin;Zhang Wenjing;Gao Bo;Song Chengyi;Han Daishu
腮腺炎病毒(MUV)对睾丸具有高度嗜性，可能导致男性不育。支持细胞是MUV感染的主要靶点。然而，Muv感染损害男性生育能力和支持细胞功能的机制尚不清楚。本研究阐明了MUV感染对血-睾丸屏障(BTB)的影响。检测MUV感染的小鼠Sertoli细胞跨上皮电阻值，并检测BTB主要蛋白的表达。我们证明了MUV感染通过降低闭锁蛋白和闭锁带水平来阻断小鼠血小管连接。TLR2−/−和TnFa−/−小鼠来源的支持细胞被分析以介导MUV诱导的损伤。MUV感染后支持细胞产生TLR2介导的肿瘤坏死因子-α破坏了血小板膜的完整性。在TLR2−/−和TnFa−/−Sertoli细胞中未观察到MUV损伤的BTB。此外，肿瘤坏死因子-α的抑制剂泊马度胺可以防止血结核对MUV感染的破坏。FITC标记的生物素示踪实验证实，体内MUV感染对BTB通透性和精子发生有一过性损害。这些结果表明，BTB的破坏可能是MUV损害男性生育能力的机制之一，其中肿瘤坏死因子-α可能在其中起关键作用。--吴华，蒋欣，高，Y.，刘伟，王芬，龚某，M，陈，R，余，X.，张伟，高，B.，宋，C.，韩，D腮腺炎病毒感染通过诱导支持细胞中肿瘤坏死因子-α破坏血-睾丸屏障。
Mumps virus (MuV) has high tropism to the testis and may lead to male infertility. Sertoli cells are the major targets of MuV infection. However, the mechanisms by which MuV infection impairs male fertility and Sertoli cell function remain unclear. The present study elucidated the effect of MuV infection on the blood-testis barrier (BTB). The transepithelial electrical resistance of MuV-infected mouse Sertoli cells was monitored, and the expression of major proteins of the BTB was examined. We demonstrated that MuV infection disrupted the BTB by reducing the levels of occludin and zonula occludens 1. Sertoli cells derived from Tlr2−/− and Tnfa−/− mice were analyzed for mediating MuV-induced impairment. TLR2-mediated TNF-α production by Sertoli cells in response to MuV infection impaired BTB integrity. MuV-impaired BTB was not observed in Tlr2−/− and Tnfa−/− Sertoli cells. Moreover, an inhibitor of TNF-α, pomalidomide, prevents the disruption of BTB in response to MuV infection. FITC-labeled biotin tracing assay confirmed that BTB permeability and spermatogenesis were transiently impaired by MuV infection in vivo. These findings suggest that the disruption of the BTB could be one of the mechanisms underlying MuV-impaired male fertility, in which TNF-α could play a critical role.—Wu, H., Jiang, X., Gao, Y., Liu, W., Wang, F., Gong, M., Chen, R., Yu, X., Zhang, W., Gao, B., Song, C., Han, D. Mumps virus infection disrupts blood-testis barrier through the induction of TNF-α in Sertoli cells.