Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection
Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection
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DOI：
10.1128/jvi.00818-14
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发表时间：
2014-08-01
影响因子：
5.4
通讯作者：
You, Dahui
中科院分区：
文献类型：
--
作者：
Cormier, Stephania A.;Shrestha, Bishwas;You, Dahui
呼吸道合胞病毒（RSV）感染是婴儿毛细支气管炎的头号原因，但由于缺乏对婴儿免疫系统的了解，目前还没有疫苗可用。使用新生小鼠模型，我们以前发现，最初感染RSV的小鼠新生儿在再感染过程中发展Th 2偏向的免疫病理生理学，我们证明了增强的白细胞介素-4受体α（IL-4 R α）在T辅助细胞的表达在这些反应中的作用。在这里，我们表明，RSV感染的新生儿诱导有限的I型干扰素（IFN）和浆细胞样树突状细胞（pDC）的反应。在新生儿RSV感染之前，IFN α（IFN-α）治疗或能够诱导IFN-α的成人pDC的过继转移降低了再感染期间的Th 2偏向性免疫发病机制。在IFN-α处理的新生小鼠中观察到病毒载量减少和Th 2细胞上IL-4 R α下调，表明双重作用机制。
Respiratory syncytial virus (RSV) infection is the number one cause of bronchiolitis in infants, yet no vaccines are available because of a lack of knowledge of the infant immune system. Using a neonatal mouse model, we previously revealed that mice initially infected with RSV as neonates develop Th2-biased immunopathophysiologies during reinfection, and we demonstrated a role for enhanced interleukin-4 receptor alpha (IL-4R alpha) expression on T helper cells in these responses. Here we show that RSV infection in neonates induced limited type I interferon (IFN) and plasmacytoid dendritic cell (pDC) responses. IFN alpha (IFN-alpha) treatment or adoptive transfer of adult pDCs capable of inducing IFN-alpha prior to neonatal RSV infection decreased Th2-biased immunopathogenesis during reinfection. A reduced viral load and downregulation of IL-4R alpha on Th2 cells were observed in IFN-alpha -treated neonatal mice, suggesting dual mechanisms of action.