Acute and chronic airway responses to viral infection: implications for asthma and chronic obstructive pulmonary disease.
Acute and chronic airway responses to viral infection: implications for asthma and chronic obstructive pulmonary disease.
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DOI：
10.1513/pats.200502-015aw
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
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作者：
Holtzman, Michael J;Tyner, Jeffrey W;Zhang, Yong
尽管已确定的和新出现的呼吸道病毒具有重大的临床影响，但宿主对这些病原体反应的一些关键方面仍需明确。在此背景下，我们针对两个主要问题：首先，控制常见呼吸道病毒感染的先天免疫机制是什么；其次，这些机制是否也会导致长期的气道疾病。利用病毒性细支气管炎的小鼠模型，我们发现抗病毒防御至少部分依赖于一个为免疫反应基因表达而特别编程的黏膜上皮细胞和巨噬细胞网络。当这个网络受损时，宿主极易受到感染，但可以对网络成分进行改造以提高对感染的抵抗力。类似的改变出现在哮喘和慢性支气管炎/慢性阻塞性肺疾病中，这表明不断改进抗病毒防御的尝试可能也会导致炎症性气道疾病。事实上，在具有遗传易感性的小鼠中，呼吸道副黏病毒会导致一种“打了就跑”的现象，即在感染清除很久之后，会出现一种永久性的气道疾病表型。这种表型可以分解为单个特征，以便更精确地确定病毒是如何重新编程宿主行为的。识别表现出异常抗病毒反应的黏膜免疫系统的特定成分，可能因此能够调整这种反应，以改善病毒感染后的急性和慢性结果。
Despite the high clinical impact of established and emerging respiratory viruses, some critical aspects of the host response to these pathogens still need to be defined. In that context, we aimed at two major issues: first, what are the innate immune mechanisms that control common respiratory viral infections; and second, whether these mechanisms also cause long-term airway disease. Using a mouse model of viral bronchiolitis, we found that antiviral defense depends at least in part on a network of mucosal epithelial cells and macrophages specially programmed for immune-response gene expression. When this network is compromised, the host is highly susceptible to infection, but network components can be engineered to provide increased resistance to infection. Similar alterations appear in asthma and chronic bronchitis/chronic obstructive pulmonary disease, suggesting that evolving attempts to improve antiviral defense may also lead to inflammatory airway disease. Indeed, in genetically susceptible mice, respiratory paramyxoviruses cause a "hit and run" phenomenon that is manifested by the development of a permanent airway disease phenotype long after the infection has cleared. The phenotype can be segregated into individual traits to achieve more precise definition of just how viruses reprogram host behavior. Identifying specific components of the mucosal immune system that manifest an aberrant antiviral response may thereby allow for adjusting this response to improve acute and chronic outcomes after viral infection.