Acute inflammatory response and remodeling of airway epithelium after subspecies B1 human adenovirus infection of the mouse lower respiratory tract
Acute inflammatory response and remodeling of airway epithelium after subspecies B1 human adenovirus infection of the mouse lower respiratory tract
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DOI：
10.1002/jmv.10475
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发表时间：
2003-10-01
影响因子：
12.7
通讯作者：
Harrod, KS
中科院分区：
文献类型：
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作者：
Kajon, AE;Gigliotti, AP;Harrod, KS
尽管B种腺病毒在严重呼吸道疾病的病因学中的作用已被充分认识，但缺乏实验性体内模型系统限制了对B种腺病毒诱导的肺炎的分子发病机制的理解。气管内滴注5 × 10（8）空斑形成单位（pfu）的腺病毒3 p和7 h导致感染小鼠肺部强烈的炎症反应。在感染后1天和2天（dpi），观察到中性粒细胞显著浸润到肺气隙中，伴随着中性粒细胞趋化因子MIP-2和KC水平的增加。在2dpi时，Ad 3 p感染的小鼠的总体组织学严重程度评分显著较高，但在其他时间点，两种病毒之间相似。在感染小鼠的近端气道中观察到气道上皮的重塑和粘液细胞化生，表明显著的上皮分化和/或损伤。促炎细胞因子白细胞介素-β（IL-1 β）、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、和白细胞介素-12（IL-12）。通过逆转录-聚合酶链反应（RT-PCR），在感染后1和2dpi，早期病毒免疫调节基因E3-15.3K和E3 gp 19 K mRNA在感染小鼠的肺中容易地被检测到，与TNF-α的峰值水平一致。而gp 19 KmRNA的检测此后下降，15.3KmRNA可检测到6dpi。我们的研究结果表明，人类腺病毒3和腺病毒7引起显着的肺部病理，诱导类似的主机在呼吸道的反应，从而验证了使用小鼠模型的研究早期病毒-宿主的相互作用，在肺部感染的腺病毒亚种B1。(C)2003 Wiley-Liss，Inc.
Despite the well-recognized role of adenoviruses of species B in the etiology of severe respiratory disease,the lack of an experimental in vivo model system has limited the understanding of the molecular pathogenesis of species B adenovirus-induced pneumonia. Intratracheal instillation of 5 x 10(8) plaque-forming units (pfu) of adenoviruses 3p and 7h resulted in a robust inflammatory response in the lungs of infected mice. A marked infiltration of neutrophils into the lung air spaces was observed at 1 and 2 days postinfection (dpi), with a concomitant increase in the levels of neutrophil chemokines MIP-2 and KC. The overall histological severity scores were significantly higher for Ad3p-infected mice at 2 dpi, but similar between the two viruses at other time points. Remodeling of the airway epithelia and mucous cell metaplasia were noted in the proximal airways of infected mice, indicating marked epithelial differentiation and/or injury. The proinflammatory cytokines interleukin-beta (IL-1beta), tumor necrosis factor-a (TNF-alpha), interferon-gamma (IFN-gamma..), and interleukin-12 (IL-12) were induced by viral infection. Expression of the early viral immunomodulatory genes E3-15.3K and E3gp19K mRNA was readily detectable in the lungs of infected mice by reverse transcription-polymerasechain reaction (RT-PCR)at 1 and 2 dpi, coinciding with the peak levels of TNF-a. While the detection of gp19K mRNA declined thereafter, 15.3K mRNA was detectable up to 6 dpi. Our results indicate that human Ad3 and Ad7 cause marked pulmonary pathology, inducing similar host responses in the respiratory tract, thus validating the use of the mouse model for the study of early virus-host interactions during lung infection by adenoviruses of subspecies B1. (C) 2003 Wiley-Liss, Inc.