BALB/c小鼠作为单纯疱疹病毒1型感染模型的免疫学分析  

Immunological evaluation of BALB/c mice as an animal model for herpes simplex virus 1infection

作　　者：张小龙[1] 汤贝贝[1] 何玉凤[1] 段永忠[1] 王丽春[1] 张志晓[1] 周巨民[2] 李琦涵[1] 

机构地区：[1]中国医学科学院北京协和医学院医学生物学研究所云南省重大传染病疫苗研发重点实验室,昆明650118 [2]中国科学院/云南省动物模型与人类疾病机理重点实验室中国科学院昆明动物研究所,昆明650223

出　　处：《微生物与感染》2017年第4期222-228,共7页Journal of Microbes and Infections

基　　金：国家自然科学基金(31670173);中国医学科学院医学与健康科技创新工程项目(2016-I2M-1-019);中国医学科学院基本科研业务费(2016ZX350072);北京协和医学院"协和青年基金"(3332016115)

摘　　要：在单纯疱疹病毒1型(herpes simplex virus type 1,HSV-1)小鼠感染及其相关研究中,临床病理和免疫学指标对其分析具有重要技术意义。本研究观察了HSV-1在不同条件下感染BALB/c小鼠后的多个免疫学指标,包括外周血单核细胞(peripheral blood mononuclear cell,PBMC)群体中树突细胞比例及功能、血清中和抗体水平、PBMC中HSV-1抗原特异性T细胞水平,以及潜伏感染期小鼠神经组织中CD8^+T细胞浸润情况。结果显示,HSV-1毒株Mckrae、17^+以角膜及滴鼻途径感染3周龄及6周龄BALB/c小鼠后,小鼠PBMC中树突细胞数量增加,并显示出刺激病毒抗原特异性T细胞增殖的能力。病毒感染后35d,小鼠PBMC中未检测到白细胞介素4(interleukin 4,IL-4)^+抗原特异性T细胞,但能检测到低水平的γ干扰素(interferonγ,IFN-γ)^+抗原特异性T细胞;小鼠血清中未检测到或仅能检测到低水平的中和抗体。HSV-1以皮下及足垫注射途径感染BALB/c小鼠90d后,足垫感染途径较皮下感染诱导出更高水平的血清中和抗体,PBMC中可检测到IL-4^+及IFN-γ^+抗原特异性T细胞,但不同毒株及小鼠周龄之间出现T细胞反应程度差异。组织病理学结果表明,各组小鼠三叉神经组织中均有CD8^+T细胞浸润。这些结果提示,不同HSV-1毒株以不同途径感染不同周龄BALB/c小鼠后,均可刺激树突细胞成熟及呈递病毒抗原,但血清中和抗体及PBMC中病毒抗原特异性T细胞水平在不同毒株、感染途径及小鼠周龄之间有差异。To investigate the immunological responses of BALB/c mice to herpes simplex virus type 1 （HSV-1） infection, the following factors were followed： strains, infect routes and mouse ages, the dendritic cells （DCs） and HSV-1 specific T cell rate and function in peripheral blood mononuclear cells （PBMCs）, serum neutralizing antibody titer, and CD8＋ T cell infiltration in nervous tissues in HSV-1-infected BALB/c mice.The results showed that 3-week-and 6-week-old BALB/c mice challenged with HSV-1 Mckrae and 17＋ strains through corneal and nasal routes led to an increased rate of DCs in PBMCs, and conferred DC capacity to stimulate HSV-1 specific T cells in vivo.At 35 d post infection, low level interferon γ （IFN-γ）＋ T cells and no interleukin 4 （IL4）＋ T cells could be detected in PBMCs, and low level neutralizing antibody was present or absent in serum.Ninety days after BALB/c mice challenged with HSV-1 through subcutaneous and foot pad injection, CD8＋ T cells could be detected in mouse trigeminal ganglia in different groups.However, HSV-1 specific IFN-γ＋ T cell and IL4＋ T cell rates showed divergence between different virus strains and mouse ages.Foot pad injection of BALB/c mice with HSV-1 could elicit higher neutralizing antibody titer compared with subcutaneous injection.This research demonstrated that, infection of different age BALB/c mice with different HSV-1 strains through different routes can stimulate comparable DC maturation and antigen presentation.

关 键 词：BALB/C小鼠 单纯疱疹病毒1型 免疫学分析 

分 类 号：R392[医药卫生—免疫学]