Relative Respiratory Syncytial Virus Cytopathogenesis in Upper and Lower Respiratory Tract Epithelium
Relative Respiratory Syncytial Virus Cytopathogenesis in Upper and Lower Respiratory Tract Epithelium
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DOI：
10.1164/rccm.201304-0750oc
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发表时间：
2013-10-01
影响因子：
24.7
通讯作者：
Power, Ultan F.
中科院分区：
文献类型：
--
作者：
Guo-Parke, Hong;Canning, Paul;Power, Ultan F.
理由：呼吸道合胞病毒（RSV）是一种主要感染气道上皮的主要病原体。大多数婴儿患有轻度上呼吸道（URT）症状，而大约三分之一的婴儿进展为下呼吸道（LRT）受累。尽管上呼吸道感染普遍存在，但对婴儿上呼吸道和下呼吸道RSV感染的相对细胞发病机制知之甚少。目的：本研究旨在比较来自同一个体的鼻源性和支气管源性上皮细胞的RSV细胞发病机制，该模型来源于分化良好的初级儿童鼻（WD-PNECs）和支气管上皮细胞（WD-PBECs）。方法：分别从鼻刷和支气管刷中产生wd - pnec和WD-PBECs，模拟感染或感染RSV BT2a。检测RSV的趋向性、感染性、细胞病理学、生长动力学、细胞脱落、细胞凋亡以及细胞因子和趋化因子的反应。测量结果和主要结果：两种培养中RSV感染仅限于根尖纤毛细胞和偶尔的非纤毛细胞，而不是杯状细胞。未引起肉眼细胞病理。感染导致子代病毒在根尖释放，根尖细胞脱落、凋亡增加，偶有合胞现象。RSV生长动力学和峰值滴度在WD-PBECs中较高，与较高的纤毛细胞含量、细胞脱落和轻微的紧密连接受损相一致。然而，促炎趋化因子反应在两种培养中是相似的。此外，RSV感染诱导了lambda IFNs，特别是IL-29。结论：与在婴儿中重现RSV发病机制的许多特征的WD-PBECs相比，RSV在WD-PNECs中诱导的细胞病变和促炎反应非常相似，尽管数量较低。WD-PNECs可为研究呼吸道合胞病毒在婴儿气道上皮中的细胞病变提供可靠的替代模型。
Rationale: Respiratory syncytial virus (RSV) is a major pathogen that primarily infects airway epithelium. Most infants suffer mild upper respiratory tract (URT) symptoms, whereas approximately one-third progress to lower respiratory tract (LRT) involvement. Despite the ubiquity of URT infection, little is known about the relative cytopathogenesis of RSV infection in infant URT and LRT.Objectives: This study aimed to compare RSV cytopathogenesis in nasal-and bronchial-derived epithelium from the same individuals using novel models derived from well-differentiated primary pediatric nasal (WD-PNECs) and bronchial epithelial cells (WD-PBECs).Methods: WD-PNECs and WD-PBECs were generated from nasal and bronchial brushes, respectively, and mock-infected or infected with RSV BT2a. RSV tropism, infectivity, cytopathology, growth kinetics, cell sloughing, apoptosis, and cytokine and chemokine responses were determined.Measurements and Main Results: RSV infection in both cultures was restricted to apical ciliated cells and occasional nonciliated cells but not goblet cells. It did not cause gross cytopathology. Infection resulted in apical release of progeny virus, increased apical cell sloughing, apoptosis, and occasional syncytia. RSV growth kinetics and peak titers were higher in WD-PBECs, coincident with higher ciliated cell contents, cell sloughing, and slightly compromised tight junctions. However, proinflammatory chemokine responses were similar for both cultures. Also, lambda IFNs, especially IL-29, were induced by RSV infection.Conclusions: RSV induced remarkably similar, albeit quantitatively lower, cytopathogenesis and proinflammatory responses in WD-PNECs compared with WD-PBECs that reproduce many hallmarks of RSV pathogenesis in infants. WD-PNECs may provide an authentic surrogate model with which to study RSV cytopathogenesis in infant airway epithelium.