项目名称: 保护性新抗原AsnC在布鲁氏菌毒力和免疫保护中的作用机制研究
项目编号: No.31272592
项目类型: 面上项目
立项/批准年度: 2013
项目学科: 农业科学
项目作者: 邱业峰
作者单位: 中国人民解放军军事医学科学院
项目金额: 81万元
中文摘要: AsnC蛋白是Lrp/AsnC家族的成员,该家族的蛋白参与细菌的氨基酸和小分子代谢物的调控,与胞内寄生菌的胞内生存和慢性感染密切相关。AsnC蛋白是我们鉴定的一个保护性新抗原。本研究拟在前期研究的基础上,分别从诱导的免疫反应和调控布鲁氏菌毒力两个方面进行研究。通过测定IgG类型及比值、IFN-γ等细胞因子的分泌、迟发型变态反应等,分析AsnC蛋白诱导的免疫反应特性,通过突变株在体外压力适应、巨噬细胞内存活、小鼠体内的生存力和慢性感染等多个层面,分析AsnC在布鲁氏菌毒力表型和慢性感染中的作用,通过转录组比较分析、RT-PCR测定基因转录等方法,分析AsnC调控的靶标基因。通过分析AsnC诱导的免疫反应的杀抑菌作用和突变株诱导免疫反应的差异,分析免疫反应与毒力间的相互关系。综合以上数据,全面阐述AsnC蛋白在毒力和免疫保护性中的作用机制,为布鲁氏菌亚单位疫苗和治疗药物的开发奠定基础。
中文关键词: 布鲁氏菌;致病性;免疫反应;;
英文摘要: AsnC is a member of the Lrp/AsnC family that involved in regulation of amino acid and small molecule metabolism, which is associated with intracellular survival and chronic infection of intracellular bacteria. AsnC is a new protective antigen identified in our previous antigen screening. In the present project, the immune responses and virulence regulation of AsnC will be systematically investigated. The IgG isotype and their ratio, secretion of IFN and TDH are analyzed to characterize its immunogenicity. The adaptation to environment, intracellular survival in macrophage and mice were analyzed, to probe into its roles in Brucella virulence. Comparative transcriptome and RT-PCR are used to analyze transcription of AsnC and its target genes. The inhibitory and killing capability of immune response for Brucella and immune reaction induction of asnC mutant are analyzed to define the interaction between immune response induction and virulence. Taken these data, the immunogenicity and protection mechanism of AsnC are evaluated, providing insight for development of new vaccine and drugs for Brucella.
英文关键词: Brucella;Pathogenesis;Immune responses;;