实用医学杂志 ›› 2021, Vol. 37 ›› Issue (8): 1000-1007.doi: 10.3969/j.issn.1006⁃5725.2021.08.008

• 基础研究 • 上一篇    下一篇

Dock2通过调节T细胞活性和抗原特异性IgG抗体的产生来控制肠道柠檬酸杆菌感染

孟凡,陈峻, 刘雨霞, 谢璐,李子俊,刘志平   

  1. 1 赣南医学院第一附属医院消化内科(江西赣州 341000);2 赣南医学院2019级研究生(江西赣州 341000), 3 赣南医学院心脑血管防治教育部重点实验室炎症与免疫中心(江西赣州 341000);4 赣南医学院基础医学 院(江西赣州 341000);5 南方医科大学第二临床分委会,广东省人民医院(广州510000)

  • 出版日期:2021-04-25 发布日期:2021-04-25
  • 通讯作者: 李子俊 E⁃mail:346503383@qq.com;刘志平 E⁃ mail:Zhiping.Liu@gmu.edu.cn。
  • 基金资助:

    国家自然科学基金(编号:31560260);江西省自 然科学基金(编号:20151BAB205061)

Dock2 controls enteric bacterial clearance through regulating T cell activity and antigen⁃specific IgG pro⁃ duction

MENG Fan,CHEN Jun,LIU Yuxia,XIE Lu,LI Zijun,LIU Zhiping.   

  1. Department of Gastroenterology the First Affiliated Hospital of Gannan Medical University,Ganzhou 341000,China;*Second Clinical Medical Colledge,South Medical University,Guangdong Province People′s Hospital,Guangzhou 510000,China

  • Online:2021-04-25 Published:2021-04-25
  • Contact: LI Zijun E⁃mail:346503383@qq.com;LIU Zhiping E⁃mail:Zhiping.Liu@gmu.edu.cn

摘要:

目的 探讨Dock2在宿主对抗柠檬酸杆菌感染的适应性免疫中的功能,研究柠檬酸杆菌感染后期淋巴细胞变化与细菌清除率之间的关系。方法 取WT及Dock2-/-小鼠灌胃感染柠檬酸杆菌,观察21 d 内感染情况,ELISA 检测21 d小鼠血清中IFN⁃γ,TNF⁃α,KC,MCP⁃1,MIP⁃2,IL⁃6和IL⁃17的蛋白表达水平及 特异抗体IgM,IgG,IgG1,IgG2b,IgG2c和IgG3的水平;流式细胞术检测淋巴T细胞及胸腺细胞情况。分离 WT Dock2-/- T 淋巴细胞通过尾静脉注射到 TCRa-/-小鼠体内,ELISA 检测 IgG,IgG1,IgG2b,IgG2c,IgG3 IgA和IgM的水平。取感染D0和D21的WT小鼠血清注射到感染柠檬酸杆菌的Dock2-/-小鼠尾静脉中后,记录存活率。结果 感染后,Dock2-/-小鼠具有更高水平的促炎细胞因子和更多的髓样细胞浸润。但是,Dock2-/- 小鼠激活的T细胞、B细胞数量减少且血清抗原特异性IgG抗体产生降低。T细胞转移和血清转移对柠檬酸杆菌诱导的结肠炎具有抑制作用。结论 Dock2对于柠檬酸杆菌感染后期宿主清除致病菌至关重要。

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Abstract:

Objective To explore the function of Dock2 in the host′s adaptive immunity against C. roden⁃ tium infection,and study the relationship between the changes of lymphocytes and bacterial clearance in the late stage of C. rodentium infection. Methods WT and Dock2⁃/⁃mice were intragastrically infected with C. rodentium to observe the infection within 21 days. ELISA was used to detected IFN⁃γ,TNF⁃α,KC,MCP⁃1 and MIP⁃2 in the sera of mice during 21 days,the protein expression levels of IL⁃6 and IL⁃17,and the levels of specific antibodies IgM,IgG,IgG1,IgG2b,IgG2c and IgG3;flow cytometry was used to detect T lymphocytes and thymocytes. The T lymphocytes isolated from WT and Dock2-/- were injected into the TCRa-/- mice by tail veins,and the levels of IgG,IgG1,IgG2b,IgG2c,IgG3,IgA and IgM were detected by ELISA. Sera of WT mice at D0 and D21 after infection were injected into the tail veins of Dock2-/- mice followed by infection,and the survival rates were recorded. Results:After C.rodentium infection,Dock2-/- mice had much more production of pro⁃ inflammatory cytokines and macrophage/neutrophil infiltration than WT mice. The mechanism of bacterial clearance disorder caused by Dock2 deletion after C. rodentium infection may be associated with the T⁃cell and B⁃cell deficiency,and reduced serum antigen⁃specific IgG antibody in Dock2-/- mice. Consistently ,T cell transfer and serum transfer has inhibitory effects on C.rodentium⁃induced colitis. Conclusion Dock2 was required for host bacterial clearance after C.roden⁃tium infection.  

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