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A range of research suggest immunopathogenesis during the occurrence of pulmonary edema in severe HFMD patients. Herein, to investigate the potential mechanism of immune dysregulation in the development of pulmonary edema upon <jats:italic>Enterovirus<\/jats:italic> (EV) infection, we established mouse infection models for <jats:italic>Enteroviruses<\/jats:italic> (EVs) including <jats:italic>Coxsackievirus<\/jats:italic> (CV) A6, <jats:italic>Enterovirus<\/jats:italic> A71 (EVA71), and CVA2 exhibiting a high incidence of pulmonary edema. We found that EVs infection induced an immune system disorder by reducing the numbers of pulmonary and circulatory T cells, B cells, macrophages, and monocytes and increasing the numbers of lung neutrophils, myeloid\u2010derived suppressor cells (MDSCs), and activated T cells. In addition, the concentrations of C\u2212X\u2212C motif chemokine ligand 1 (CXCL\u20101), tumor necrosis factor\u2010alpha, monocyte chemoattractant protein\u20101, and interleukin 6 were increased in EV\u2010infected lungs. Moreover, we found that EVs replication in mice lungs lead to apoptosis of lung cells and degradation of tight junction proteins. In conclusion, EVs infection likely triggered a complexed immune defense mechanism and caused dysregulation of innate immune cells (MDSCs, neutrophils, monocytes, and macrophages) and adaptive cellular immunity (B cells, T cells). This dysregulation increased the release of cytokines and other inflammatory factors from activated immune\u2010related cells and caused lung barrier damage and pulmonary edema.<\/jats:p>","DOI":"10.1002\/jmv.28454","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T10:16:36Z","timestamp":1672827396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Local immune dysregulation and subsequent inflammatory response contribute to pulmonary edema caused by <i>Enterovirus<\/i> infection in mice"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4895-4316","authenticated-orcid":false,"given":"Tiantian","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Epidemiology, College of Public Health Zhengzhou University Zhengzhou 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