结核分枝杆菌通过诱导宿主产生S100A8/A9促进T细胞死亡的机制研究  

Mycobacterium tuberculosis promotes T lymphocyte death by S100A8/A9 produced by host cells

作　　者：孙月华 杨玉玲 李林昊 屈沛杰 柳卫凰 章晓联 潘勤 SUN Yue-hua;YANG Yu-ling;LI Lin-hao;QU Pei-jie;LIU Wei-huang;ZHANG Xiao-lian;PAN Qin(Department of Anatomy,Wuhan University School of Basic Medical Sciences Hubei Province Key Laboratory of Allergy and Immunology,Wuhan 430071,Hubei,China)

机构地区：[1]武汉大学基础医学院人体解剖学教研室湖北省过敏及免疫相关疾病重点实验室,湖北武汉430071

出　　处：《中国病原生物学杂志》2022年第1期49-54,共6页Journal of Pathogen Biology

基　　金：国家自然科学基金面上项目(No.81971908)。

摘　　要：目的探讨结核分枝杆菌(Mtb)诱导宿主产生的S100钙结合蛋白A8/A9复合物(S100A8/A9)促进T细胞死亡的作用及机制。方法灭活毒性Mtb H37Rv(iMtb H37Rv)与野生型(WT)小鼠全脾细胞体外共同培养不同时间,通过流式细胞术得到S100A8与S100A9的表达差异以及产生S100A8/A9的细胞群。Mtb H37Rv体外诱导WT和S100a9^(-/-)小鼠全脾细胞,通过流式细胞术检测S100A8/A9对CD4^(+)T细胞死亡的影响。采用不同浓度S100A8/A9与人T淋巴细胞系Jurkat细胞共同培养、S100A8/A9与细胞共培养不同时间或是S100A8、S100A9单体以及S100A8/A9复合物与细胞共同培养,通过流式细胞术得到S100A8/A9对Jurkat细胞死亡的影响。通过Western blot检测不同细胞表面TLR4的表达差异。封闭Jurkat细胞表面TLR4受体后与S100A8/A9共同培养,通过流式细胞术得到Jurkat细胞死亡的变化。结果与对照组相比,iMtb H37Rv能诱导脾细胞产生更多的S100A8和S100A9蛋白。S100A8/A9能促进小鼠CD4^(+)T细胞死亡。低剂量的S100A8/A9复合物能诱导Jurkat细胞死亡,且S100A8和S100A A9单体无以上作用。S100A8/A9复合物诱导T细胞死亡为TLR4非依赖通路。结论Mtb通过诱导宿主产生S100A8/A9并促进T细胞死亡。Objective To investigate the effects of S100 calcium binding protein A8/A9 heterodimer(S100 A8/A9)induced by Mycobacterium tuberculosis(Mtb)on T cell death.Methods The murine wildtype(WT)splenocytes were incubated with inactivated Mtb H37 Rv(IMtbH37 Rv)in vitro for various time points.The expression differences of S100 A8 and S100 A9 and the S100 A8/A9-producing cells were obtained by flow cytometry.The WT and S100a9^(-/-)mice splenocytes were induced by IMtbH37 Rv in vitro,and the effects of S100 A8/A9 on the CD4^(+)T cell death was detected by flow cytometry.The effects of S100 A8/A9 on the death of human T cell line Jurkat cells was assessed by incubating the cells with different concentration of S100 A8/A9 or with S100 A8/A9 for different time points.S100 A8,S100 A9 monomer and S100 A8/A9 heterodimer were employed to demonstrate the heterodimer activity of induction of cell death.The expression effects of TLR4 on different cell surfaces was detected by Western blot.After blocking the TLR4 on the surface of Jurkat cells,it was incubated with S100 A8/A9.The differences of cell death were obtained by flow cytometry.Results iMtb H37 Rv induced murine splenocytes to produce more S100 A8 and S100 A9 proteins compared with the control group.S100 A8/A9 heterodimer rather than S100 A8 and S100 A9 monomers promoted the death of CD4^(+)T cells.S100 A8/A9 induced T cell death irrespective of TLR4 pathway.Conclusion Mtb-induced S100 A8/A9 promotes T cell death.

关 键 词：S100A8/A9 CD3^(+)CD4^(+)T细胞 Mtb H37Rv 细胞死亡 

分 类 号：R378.991[医药卫生—病原生物学]