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The fatality rate of JE is 20%, and nearly half of the surviving patients develop neuropsychiatric sequelae. Axl is a receptor tyrosine kinase that plays multiple roles in flaviviral infections. Currently, the involvement of Axl in JEV infection remains enigmatic. In this study, we demonstrate that Axl impedes the pathogenesis of severe JE in mice by maintaining blood-brain-barrier (BBB) integrity and restricting viral neuroinvasion. Furthermore, serum IL-1\u03b1 is a key mediator of this process and is primarily released by JEV-infected pyroptotic macrophages to elicit BBB breakdown, while an IL-1\u03b1 antagonist can effectively reduce the incidence of severe JE. Our work uncovers the protective role of Axl in antagonizing severe JE and shows that the use of an IL-1\u03b1 antagonist may be a promising tactic to prevent severe JE.<\/jats:p>","DOI":"10.1128\/jvi.00602-20","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T10:26:50Z","timestamp":1593426410000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Axl Deficiency Promotes the Neuroinvasion of Japanese Encephalitis Virus by Enhancing IL-1\u03b1 Production from Pyroptotic Macrophages"],"prefix":"10.1128","volume":"94","author":[{"given":"Zhao-Yang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Da","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, 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