Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease
Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease
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DOI：
10.1002/path.4660
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发表时间：
2016-02-01
影响因子：
7.3
通讯作者：
Bem, Reinout A.
中科院分区：
文献类型：
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作者：
Cortjens, Bart;de Boer, Onno J.;Bem, Reinout A.
人呼吸道合胞病毒（RSV）是全球幼儿严重下呼吸道疾病（LRTD）的最重要原因。肺部广泛的中性粒细胞积聚和富含DNA的粘液栓阻塞小气道是严重RSV-LRTD的特征。活化的中性粒细胞可以释放中性粒细胞胞外陷阱（NET），即覆盖有抗菌蛋白的DNA胞外网络，作为对抗病原体的第一线防御的一部分。NET可以捕获和消除微生物;然而，大量的NET形成也可能导致气道阻塞。在这项研究中，我们研究了NETs是否由RSV诱导，并探讨了其潜在的体外抗病毒作用。其次，我们研究了NET形成在体内严重RSV-LRTD的婴儿和牛RSV-LRTD的小牛，通过检查支气管肺泡灌洗液和肺组织切片，分别。NET可视化肺细胞学和组织样本的DNA和免疫染色，使用瓜氨酸化组蛋白H3，弹性蛋白酶和髓过氧化物酶的抗体。RSV能够在体外诱导人中性粒细胞形成NET。此外，NET能够捕获RSV，从而排除病毒颗粒与靶细胞的结合并防止感染。在患有严重RSV-LRTD的儿童中证实了气道和肺部形成NET的证据。对RSV-LRTD小牛进行的详细组织病理学检查显示，无论是否存在捕获的病毒抗原，在阻塞气道的致密栓塞中均形成了广泛的NET。总之，这些结果表明，尽管NET捕获病毒颗粒，但它们在严重RSV-LRTD期间的过度形成有助于气道阻塞。版权所有（c）2015大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
Human respiratory syncytial virus (RSV) is the most important cause of severe lower respiratory tract disease (LRTD) in young children worldwide. Extensive neutrophil accumulation in the lungs and occlusion of small airways by DNA-rich mucus plugs are characteristic features of severe RSV-LRTD. Activated neutrophils can release neutrophil extracellular traps (NETs), extracellular networks of DNA covered with antimicrobial proteins, as part of the first-line defence against pathogens. NETs can trap and eliminate microbes; however, abundant NET formation may also contribute to airway occlusion. In this study, we investigated whether NETs are induced by RSV and explored their potential anti-viral effect in vitro. Second, we studied NET formation in vivo during severe RSV-LRTD in infants and bovine RSV-LRTD in calves, by examining bronchoalveolar lavage fluid and lung tissue sections, respectively. NETs were visualized in lung cytology and tissue samples by DNA and immunostaining, using antibodies against citrullinated histone H3, elastase and myeloperoxidase. RSV was able to induce NET formation by human neutrophils in vitro. Furthermore, NETs were able to capture RSV, thereby precluding binding of viral particles to target cells and preventing infection. Evidence for the formation of NETs in the airways and lungs was confirmed in children with severe RSV-LRTD. Detailed histopathological examination of calves with RSV-LRTD showed extensive NET formation in dense plugs occluding the airways, either with or without captured viral antigen. Together, these results suggest that, although NETs trap viral particles, their exaggerated formation during severe RSV-LRTD contributes to airway obstruction. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.