Mast cells contribute to Enterovirus 71 infection-induced pulmonary edema in neonatal mice



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-α (TNF-α), 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.

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We thank Yinming Liang of Laboratory of Genetic Regulators in the Immune System, School of Laboratory Medicine, Xinxiang Medical University for helping us perform Flow Cytometry analysis. We thank Po-Hsun Huang of Department of Mechanical Engineering and Materials Science, Duke University for article’s edit. This work was funded by the National Natural Science Foundation of China (81172740); National Natural Science Foundation of China (81573205); Key scientific research projects in Colleges and Universities of Henan Province (15A330003); Outstanding doctoral thesis training fund of Zhengzhou University.

Author information


  1. Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China

    • Yuefei Jin
    • , Chao Zhang
    • , Rongguang Zhang
    • , Shuaiyin Chen
    • , Dejian Dang
    • , Peng Zhang
    • , Yuanlin Xi
    •  & Guangcai Duan
  2. Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang, Henan, People’s Republic of China

    • Hui Wang
    • , Xiangpeng Wang
    • , Rongguang Zhang
    • , Jingchao Ren
    •  & Weidong Wu
  3. Research Center for Immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China

    • Hui Wang
    •  & Xiangpeng Wang
  4. School of Public Health, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China

    • Guangyuan Zhou
    • , Jingchao Ren
    •  & Weidong Wu
  5. Department of Oncology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China

    • Lu Chen
  6. Department of Immunology, Duke University Medical Center, Durham, NC, United States of America

    • Weiguo Zhang


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The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Guangcai Duan.

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