Dept of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma and Centre for Respiratory Infection, Imperial College London, London, UK.
Eur Respir J. 2012 Mar;39(3):712-20. doi: 10.1183/09031936.00099811. Epub 2011 Aug 18.
The cytokine interleukin (IL)-15, major histocompatibility complex (MHC) class I molecules and MHC class I chain-related proteins (MIC) A and B are involved in cellular immune responses to virus infections but their role in respiratory syncytial virus (RSV) infection has not been studied. We aimed to determine how RSV infection modulates IL-15 production, MHC class I and MICA expression in respiratory epithelial cells, the molecular pathways implicated in virus-induced IL-15 production and how interferon (IFN)-γ alters RSV-induced IL-15 production and MHC class I and MICA expression. We infected respiratory epithelial cell lines (A549 and BEAS-2B cells) and primary bronchial epithelial cells with RSV and measured production of IL-15, expression of MHC I and MICA and the role of the transcription factor nuclear factor (NF)-κB. We report here that RSV increases IL-15 in respiratory epithelial cells via virus replication and NF-κB-dependent mechanisms. Furthermore, RSV infection of epithelial cells upregulated cell surface expression of MICA and levels of soluble MICA. IFN-γ upregulated RSV induction of soluble IL-15 but inhibited induction of MICA. Upregulation of IL-15, MHC I and MICA are likely to be important mechanisms in activating immune responses to RSV by epithelial cells.
细胞因子白细胞介素 (IL)-15、主要组织相容性复合体 (MHC) Ⅰ类分子和 MHC Ⅰ类链相关蛋白 (MIC) A 和 B 参与细胞免疫对病毒感染的反应，但它们在呼吸道合胞病毒 (RSV) 感染中的作用尚未研究。我们旨在确定 RSV 感染如何调节呼吸道上皮细胞中 IL-15 的产生、MHC I 和 MICA 的表达，涉及病毒诱导的 IL-15 产生的分子途径，以及干扰素 (IFN)-γ 如何改变 RSV 诱导的 IL-15 产生和 MHC I 和 MICA 的表达。我们用 RSV 感染呼吸道上皮细胞系（A549 和 BEAS-2B 细胞）和原代支气管上皮细胞，测量 IL-15 的产生、MHC I 和 MICA 的表达以及转录因子核因子 (NF)-κB 的作用。我们在这里报告，RSV 通过病毒复制和 NF-κB 依赖性机制增加呼吸道上皮细胞中的 IL-15。此外，上皮细胞中 RSV 的感染上调了 MICA 的细胞表面表达和可溶性 MICA 的水平。IFN-γ 上调 RSV 诱导的可溶性 IL-15，但抑制 MICA 的诱导。IL-15、MHC I 和 MICA 的上调可能是上皮细胞激活对 RSV 免疫反应的重要机制。
