Mast cells contribute to Enterovirus 71 infection- induced pulmonary edema in neonatal mice
Mast cells contribute to Enterovirus 71 infection- induced pulmonary edema in neonatal mice
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肥大细胞导致新生小鼠肠道病毒 71 感染引起的肺水肿。
DOI：
10.1038/s41374-018-0075-y
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发表时间：
2018-08-01
影响因子：
5
通讯作者：
Duan, Guangcai
中科院分区：
文献类型：
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作者：
Jin, Yuefei;Zhang, Chao;Duan, Guangcai
肠病毒71型感染已被广泛认为是严重手足口病的主要原因，可迅速导致致命的肺水肿。在本研究中，我们建立了一种EV 71感染的小鼠模型，该模型表现出高发生率的严重症状和肺水肿。EV 71感染小鼠后，在脑、肺和骨骼肌中发现肥大细胞（MC）聚集、活化和过敏性炎症，尤其是在小鼠的肺中。组胺、血小板活化因子（PAF）、白细胞介素（IL）-4、IL-5、IL-13、肿瘤坏死因子-α（TNF-α）、一氧化氮（NO）、内分泌腺衍生的血管内皮生长因子（EG-VEGF）和去甲肾上腺素（NA）的水平在EV 71感染的肺中升高。此外，EV 71感染减少了肺T细胞、树突状细胞（DC）和单核细胞的数量，并增加了肺嗜酸性粒细胞、TCFs和MC的数量。MC数量和类胰蛋白酶在靶器官或组织中的表达呈现出从对照组到重度小鼠增加的趋势。脑（r = 0.701，P = 0.003）、肺（r = 0.802，P < 0.0001）、骨骼肌（r = 0.737，P = 0.001）的MC数与平均临床评分呈正相关。因此，我们的研究结果表明，MC参与了EV 71感染时的肺水肿。
Enterovirus (EV) 71 infection has been widely acknowledged as the leading cause of severe hand, foot and mouth disease (HFMD), which may rapidly lead to fatal pulmonary edema. In this study, we established a mouse model for EV71 infection exhibiting high incidence of severe symptoms with pulmonary edema. Mast cells (MCs) accumulation, activation and allergic inflammation were found in the brains, lungs and skeletal muscle of mice after EV71 infection, especially in the lungs of mice. Levels of histamine, platelet-activating factor (PAF), interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor-a (TNF-alpha), nitric oxide (NO), endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and noradrenaline (NA) were increased in EV71-infected lungs. In addition, EV71 infection reduced the number of pulmonary T cells, dendritic cells (DCs) and monocytes, and increased the number of lung eosinophils, Tregs and MCs. MCs number and tryptase expression in target organs or tissues posed a trend towards an increase from control to severe mice. There were positive correlations between MCs number in the brains (r = 0.701, P = 0.003), lungs (r = 0.802, P < 0.0001), skeletal muscles (r = 0.737, P = 0.001) and mean clinical score. Thus, our results suggested that MCs contributed to the pulmonary edema during EV71 infection.