Human Metapneumovirus (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects human lung microvascular endothelial cells (L-HMVECs). The release of infectious virus occurs for up to more than 30 days of culture without producing overt cytopathic effects and medium derived from persistently HMPV-infected L-HMVECs (secretome) induced monocyte-derived DCs to prime naïve CD4 T-cells toward a Th2 phenotype. Moreover, we demonstrated that infected secretomes trigger DCs to up-regulate OX40L expression and OX40L neutralization abolished the pro-Th2 effect that is induced by HMPV-secretome. We clarified secretome from HMPV by size exclusion and ultracentrifugation with the aim to characterize the role of viral particles in the observed pro-Th2 effect. In both cases, the percentage of IL-4-producing cells and expression of OX40L returned at basal levels. Finally, we showed that HMPV, per se, could reproduce the ability of secretome to prime pro-Th2 DCs. These results suggest that HMPV, persistently released by L-HMVECs, might take part in the development of a skewed, pro-Th2 lung microenvironment.

中文翻译：

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人类偏肺病毒在肺微血管内皮细胞中建立持久性感染并引发Th2倾斜的免疫反应。

人间质肺病毒（HMPV）是下呼吸道感染的主要原因。有人假设HMPV感染会改变树突状细胞（DC）的免疫反应。然而，关于受感染肺内HMPV发病机制的许多问题仍未得到解答。在这里，我们显示HMPV生产性感染人肺微血管内皮细胞（L-HMVECs）。传染性病毒的释放在长达30天以上的培养中均未产生明显的细胞病变作用，并且源于持续受HMPV感染的L-HMVEC（分泌基因组）诱导的单核细胞衍生DC产生的培养基将未成熟的CD4 T细胞引向Th2表型。 。此外，我们证明感染的分泌组触发DC来上调OX40L表达，而OX40L中和则消除了HMPV分泌组诱导的促Th2效应。我们通过大小排阻和超速离心澄清了HMPV的分泌蛋白组，目的是表征病毒颗粒在观察到的促Th2效应中的作用。在这两种情况下，产生IL-4的细胞百分比和OX40L的表达均恢复到基础水平。最后，我们证明了HMPV，本身，可以复制促分泌素组促Th2亲DC的能力。这些结果表明，由L-HMVEC持续释放的HMPV可能参与了偏斜的Th2亲肺微环境的发展。