Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease

中性粒细胞胞外陷阱 支气管肺泡灌洗 中性粒细胞弹性蛋白酶 病毒 免疫学 生物 呼吸道 呼吸系统 免疫染色 病理 医学 病毒学 炎症 免疫组织化学 内科学 解剖
作者
Bart Cortjens,Onno J. de Boer,Rineke de Jong,A.F.G. Antonis,Yanaika S. Sabogal Piñeros,René Lutter,Job B. M. van Woensel,A. Reinout
标识
DOI:10.1002/path.4660
摘要

Abstract 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 © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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