Axl Alleviates Neuroinflammation and Delays Japanese Encephalitis Progression in Mice

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus,which causes the most commonly diagnosed viral encephalitis named Japanese encephalitis (JE) in the world with an unclear pathogenesis.Axl,a receptor tyrosine kinase from TAM family,plays crucial role in many inflammatory diseases.We have previously discovered that Axl deficiency resulted in more severe body weight loss in mice during JEV infection,which we speculate is due to the anti-inflammatory effect of Axl during JE.Currently,the role of Axl in regulating the neuroinflammation and brain damage during JE has not been investigated yet.In this study,by using Axl deficient and heterozygous control mice,we discovered that Axl deficient mice displayed accelerated JE progression and exacerbated brain damage characterized by increased neural cell death,extended infiltration of inflammatory cells,and enhanced production of pro-inflammatory cytokines,in comparison to control mice.Additionally,consistent with our previous report,Axl deficiency had no impact on the infection and target cell tropism of JEV in brain.Taken together,our results suggest that Axl plays an anti-inflammatory and neuroprotective role during the pathogenesis of JE.