蝙蝠蛾被毛孢菌丝体通过激活TLR2、TLR4和Dectin-1诱导Th1型免疫反应  

Mycelium of Hirsutella hepiali Chen et Shen induces maturation of dendritic cells and Th1-type immune response

作　　者：陈志蓉[1] 刘含智[1] 杨红振[1] 吕晓希[1] 米粟[1] 胡卓伟[1] 

机构地区：[1]中国医学科学院药物研究所,北京100050

出　　处：《中国免疫学杂志》2009年第10期895-902,共8页Chinese Journal of Immunology

基　　金：国家"973"计划项目(2006CB503808);国家自然科学基金面上项目(30672468);博士点基金(20070023035)资助

摘　　要：目的:研究蝙蝠蛾被毛孢菌丝体(MHCS)对抗原呈递细胞树突状细胞(Dendritic cells,DCs)成熟和功能的调节作用。方法:利用流式细胞术、实时荧光定量PCR、Western blot和混合淋巴细胞培养等实验方法,检测了MHCS对DCs成熟和功能相关表面分子、细胞因子表达以及Toll样受体(TLR)2、TLR4和Dectin-1相关信号转导通路蛋白活性的调节作用。结果:MHCS显著上调DCs表面分子CD11c、MHCⅠ和MHCⅡ、辅助刺激分子CD40、CD80和CD86以及模式识别受体TLR2、TLR4和Dectin-1的表达;促进Th1型细胞因子IL-12产生,抑制Th2型细胞因子IL-10、IL-13和TGF-β1产生;诱导TAK1和IRF3磷酸化活性增加。MHCS也显著刺激幼稚型Th细胞增殖,诱导幼稚型Th细胞向Th1方向分化。利用中和性抗体,分别阻断DCs细胞TLR2、TLR4或Dectin-1活性,可部分抑制MHCS诱导的DCs成熟。结论:MHCS能促进DCs成熟,诱导Th1型免疫反应。MHCS的这些作用与其激活模式识别受体TLR2、TLR4或Dectin-1有关。Objective：To investigate regulatory effects and mechanisms of Mycelium of Hirsutella hepiali Chen et Shen （MHCS） on the maturation and functions of dendritic cells （DCs）. Methods：Flow cytometry, real-time PCR, Western blot and mixed lymphocyte reaction were utilized to detect the effects of MHCS on the expressions of surface molecules and cytokines on/in DCs, and the alteration of Toll like receptor （TLR） 2, TLR4 or dectin-1 signaling pathways. Results： MHCS significantly up-regulated the expression of DC surface molecules, including CD11c, MHCⅠ and MHCⅡ , costimulators including CD40, CD80 and CD86 as well as PRRs, such as TLR2,TLR4 and Dectin-1. MHCS also enhanced the expression of Thl-type cytokine IL-12 and inhibited the expression of Th2-type cytokines IL-10, IL-13 and TGF-β1, and induced the expression and phosphorylation of TAK1 and IRF3. Additionally, MHCS-maturated DCs markedly promoted the proliferation of naive T cells and resulted in Thl-dominant immune responses. Importantly, neutralizing antibodies to TLR2, TLR4 or Dectin-1, partially blocked the stimulatory effects of MHCS on the expressions of surface molecules associated with the maturation of DCs. Conclusion： MHCS promotes the maturation of DCs and induces Thl-dominant immune responses partially via activation of TLR2, TLR4, or Dectin-1.

关 键 词：蝙蝠蛾被毛孢菌丝体 树突状细胞 Th1型免疫反应 模式识别受体 

分 类 号：R575[医药卫生—消化系统]