The protective role of Mertk in JEV-induced encephalitis by maintaining the integrity of blood–brain barrier

IF 4 3区 医学 Q2 VIROLOGY
Chuanyu Luo, Mengyuan Li, Peiyu Bian, Jiali Yang, Xiamei Liao, Yangchao Dong, Chuantao Ye, Fanglin Zhang, Xin Lv, Qianqian Zhang, Yingfeng Lei
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Abstract

Japanese encephalitis is an acute infectious disease of the central nervous system caused by neurotropic Japanese encephalitis virus (JEV). As a member of TAM (Tyro3, Axl and Mertk) family, Mertk has involved in multiple biological processes by engaging with its bridging ligands Gas6 and Protein S, including invasion of pathogens, phagocytosis of apoptotic cells, inflammatory response regulation, and the maintenance of blood brain barrier (BBB) integrity. However, its role in encephalitis caused by JEV infection has not been studied in detail. Here, we found that Mertk−/− mice exhibited higher mortality and more rapid disease progression than wild-type mice after JEV challenge. There were no significant differences in viral load and cytokines expression level in peripheral tissues between Wild type and Mertk−/− mice. Furthermore, the absence of Mertk had little effect on the inflammatory response and immunopathological damage while it can cause an increased viral load in the brain. For the in vitro model of BBB, Mertk was shown to maintain the integrity of the BBB. In vivo, Mertk−/− mice exhibited higher BBB permeability and lower BBB integrity. Taken together, our findings demonstrate that Mertk acts as a protective factor in the development of encephalitis induced by JEV infection, which is mainly associated with its beneficial effect on BBB integrity, rather than its regulation of inflammatory response.
Mertk 通过维持血脑屏障的完整性在 JEV 引起的脑炎中发挥保护作用
日本脑炎是由日本脑炎病毒(JEV)引起的中枢神经系统急性传染病。作为 TAM(Tyro3、Axl 和 Mertk)家族的成员,Mertk 通过与其桥接配体 Gas6 和蛋白 S 结合参与多种生物过程,包括病原体入侵、吞噬凋亡细胞、炎症反应调节和维持血脑屏障(BBB)完整性。然而,它在 JEV 感染引起的脑炎中的作用尚未得到详细研究。在这里,我们发现与野生型小鼠相比,Mertk-/-小鼠在接受 JEV 挑战后表现出更高的死亡率和更快的疾病进展。野生型小鼠和 Mertk-/- 小鼠外周组织中的病毒载量和细胞因子表达水平没有明显差异。此外,缺失 Mertk 对炎症反应和免疫病理损伤的影响很小,但会导致脑内病毒载量增加。在 BBB 体外模型中,Mertk 被证明能维持 BBB 的完整性。在体内,Mertk-/-小鼠表现出更高的生物BB通透性和更低的生物BB完整性。综上所述,我们的研究结果表明,Mertk 在 JEV 感染诱发脑炎的过程中起着保护作用,这主要与其对 BBB 完整性的有益作用有关,而非其对炎症反应的调节作用。
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来源期刊
Virology Journal
Virology Journal 医学-病毒学
CiteScore
7.40
自引率
2.10%
发文量
186
审稿时长
1 months
期刊介绍: Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
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