Plasticity and Virus Specificity of the Airway Epithelial Cell Immune Response during Respiratory Virus Infection
Plasticity and Virus Specificity of the Airway Epithelial Cell Immune Response during Respiratory Virus Infection
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DOI：
10.1128/jvi.06757-11
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发表时间：
2012-05-01
影响因子：
5.4
通讯作者：
Flano, Emilio
中科院分区：
文献类型：
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作者：
Ioannidis, Ioannis;McNally, Beth;Flano, Emilio
呼吸道上皮细胞(AECs)是呼吸道的第一道防线，是呼吸道病毒的主要靶点。在这里，我们使用寡核苷酸和蛋白质阵列，分析了原代培养的人AEC感染流感病毒和呼吸道合胞病毒(RSV)的情况，表明AEC的免疫反应在数量和质量上都是病毒特异性的。流感病毒诱导和非RSV诱导的差异表达基因包括干扰素B1、III型干扰素(IL-28A、IL-28B和IL-29)、白介素IL-6、IL-1A、IL-1B、IL-23A、IL-17C和IL-32以及趋化因子(CCL2、CCL8和CXCL5)。缺乏I型干扰素或STAT1信号会减少呼吸道上皮细胞因子和趋化因子的表达和分泌。在感染期间，我们还观察到人和小鼠血管内皮细胞分泌细胞因子和趋化因子的强烈基侧极化。重要的是，人血管内皮细胞对流感病毒或RSV的抗病毒反应分别与从急性流感或RSV毛细支气管炎患者分离的外周血单个核细胞(PBMC)获得的感染特征相关。IFI27(也称为ISG12)在AEC和PBMC中都被认为是呼吸道病毒感染的生物标志物。此外，PBMCs转录紊乱的程度与临床疾病严重程度相关。我们的结果表明，人类呼吸道上皮细胞启动了病毒特异性的免疫反应，这可能决定了随后的系统免疫反应，并提示呼吸道合胞病毒感染后上皮免疫介质的缺乏可能有助于解释对病毒的系统免疫不足。
Airway epithelial cells (AECs) provide the first line of defense in the respiratory tract and are the main target of respiratory viruses. Here, using oligonucleotide and protein arrays, we analyze the infection of primary polarized human AEC cultures with influenza virus and respiratory syncytial virus (RSV), and we show that the immune response of AECs is quantitatively and qualitatively virus specific. Differentially expressed genes (DEGs) specifically induced by influenza virus and not by RSV included those encoding interferon B1 (IFN-B1), type III interferons (interleukin 28A [IL-28A], IL-28B, and IL-29), interleukins (IL-6, IL-1A, IL-1B, IL-23A, IL-17C, and IL-32), and chemokines (CCL2, CCL8, and CXCL5). Lack of type I interferon or STAT1 signaling decreased the expression and secretion of cytokines and chemokines by the airway epithelium. We also observed strong basolateral polarization of the secretion of cytokines and chemokines by human and murine AECs during infection. Importantly, the antiviral response of human AECs to influenza virus or to RSV correlated with the infection signature obtained from peripheral blood mononuclear cells (PBMCs) isolated from patients with acute influenza or RSV bronchiolitis, respectively. IFI27 (also known as ISG12) was identified as a biomarker of respiratory virus infection in both AECs and PBMCs. In addition, the extent of the transcriptional perturbation in PBMCs correlated with the clinical disease severity. Our results demonstrate that the human airway epithelium mounts virus-specific immune responses that are likely to determine the subsequent systemic immune responses and suggest that the absence of epithelial immune mediators after RSV infection may contribute to explaining the inadequacy of systemic immunity to the virus.