在JEV感染期间,TLR9促进了单细胞髓衍生抑制细胞的诱导
Tingting Lian1, Weijia Zhang1, Haoran Su1
1National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan 430070, China; International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan 430070, China.
日本脑炎病毒 (JEV) 感染导致线粒体损伤,激活托尔类受体9 (TLR9). 这一途径驱动了髓质衍生抑制细胞 (MDSCs) 的扩张,损害了免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 骨髓衍生抑制细胞 (MDSC) 是不成熟的骨髓细胞,可以抑制免疫反应.
- 在日本脑炎病毒 (JEV) 感染后,脏中MDSC积累对免疫抑制至关重要.
- 对于JEV诱导MDSCs的确切机制尚不清楚.
研究的目的:
- 阐明JEV诱导的MDSC激活背后的机制.
- 研究线粒体损伤和托尔类受体9 (TLR9) 在JEV诱导的MDSC诱导中的作用.
主要方法:
- 在小鼠模型中的JEV感染.
- 对线粒体损伤和线粒体DNA (mtDNA) 释放的分析.
- 评估TLR9激活及其下游影响.
- 在体外和体内评估M-MDSC种群和抑制功能.
- 在免疫细胞上测量MHC II和CD28表达.
- 在TLR9缺乏的小鼠中监测生存率.
主要成果:
- 致病病毒感染诱导线粒体损伤,导致mtDNA释放和随后的TLR9激活.
- 由于TLR9缺乏,M-MDSC种群及其抑制功能显著减少.
- 在TLR9-/-小鼠中减少的M-MDSC与抗原呈现细胞上增加的MHC II和T细胞上增加的CD28相关.
- TLR9-/-小鼠在感染JEV后的生存率显著增加.
结论:
- 线粒体损伤和TLR9激活是JEV感染期间诱导M-MDSC的关键媒介.
- 准线粒体损伤-TLR9-MDSC轴可能提供针对JEV的治疗策略.
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