| 题名 | 女性生殖道共生菌诱导Langerhans细胞特异性C型凝集素受体Langerin（CD207）表达的研究 |
| 作者 | 郎丰超 |
| 学位类别 | 硕士 |
| 答辩日期 | 2011-05 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 张华堂 |
| 关键词 | C型凝集素受体 (CLR) 共生菌/乳杆菌 树突状细胞/Langerhans细胞 粘膜免疫疫苗递送系统 |
| 其他题名 | Effects of Vaginal Commensal Bacteria on Expression of Langerhans Cells-Specific C-Type Lectin Receptors (CLRs) |
| 学位专业 | 生物化学与分子生物学 |
| 中文摘要 | C型凝集素受体 (C-Type Lectin Receptors, CLRs) 是一类重要的模式识别受体 (Pattern Recognition Receptor, PRR)，可以识别广泛的病原体，在树突状细胞 (Dendritic Cells, DCs) 表面有大量表达。而DC前体细胞在不同刺激下表达不同的CLR，对HIV-1能否建立感染及其体内播散具有决定性的作用。因此，通过分析DC表达CLR的类别和水平，可以评价粘膜投送载体对HIV-1感染和播散的直接影响，可为粘膜疫苗、佐剂和药物的体外研究和安全评价，提供新的模式和指标。 本论文之前的研究表明，女性生殖道特有的共生菌能够刺激DC前体细胞THP-1表达CD1a、CD324、CCR6等与Langerhans细胞 (LC) 相关的表面标志。而Langerin/CD207是LC特有的、更为特异的CLR，能够以高亲和力与HIV-1结合，从而捕获和灭活病毒，遏止其感染和传播。因此，本研究拟针对实验室已分离鉴定的6种生殖道共生菌对Langerin/CD207的诱导表达进行探讨。 结果表明，L. crispatus可以刺激THP-1细胞高水平表达Langerin/CD207，伴有吞噬能力的明显上调及Th1类细胞因子的表达，提示L. crispatus能够诱导具有功能的LC，可以通过Langerin/CD207及免疫调控作用遏止HIV-1病毒感染和体内播散。因此，女性生殖道特有的共生菌可以作为粘膜免疫疫苗递送载体菌株进行进一步的深入研究。 在此基础上，我们进一步分析比较了其它5个菌株对THP-1的作用和影响，发现在不同菌株刺激后，THP-1细胞的形态、5种凝集素分子、DC相关表面分子的表达和吞噬功能等多方面均有差异，提示不同菌株能否作为递送系统需要进一步评价和筛选。 综上，本研究在THP-1体系中筛选出能够促进Langerin/CD207表达及免疫调控功能的菌苗，为筛选和评价女性生殖道定点递送体系以及在单核细胞中进行验证奠定了基础，同时也有助于根据已知的机理建立恰当的体外评价体系、从而前瞻性地判断粘膜免疫递送系统本身对病毒感染和播散的直接作用。 |
| 英文摘要 | C-type lectin receptors (CLRs) are an important family of pattern recognition receptors (PRR) that specifically recognize a variety of pathogens. Distinct CLRs which play a key role in the establishment and dissemination of HIV-1 infection in vivo, are expressed abundantly on DCs after different stimulations. Through analyzing CLR expression, we can evaluate the direct effect on HIV-1 infection and spread by mucosal delivery systems, providing a new model and standard for research in vitro and safety evaluation of mucosal vaccine, adjuvant and drug. Our previous work showed that vaginal lactobacilli can stimulate DCs precursors THP-1 to express Langerhans cells marker molecules, such as CD1a, CD324 and CCR6. And Langerin/CD207, as more specific and characteristic CLR for LC, can capture HIV-1 through its high-affinity binding, scavenge virus and prevent virus infection and dissemination. So, in the present study we will research the induction of expression of Langerin/CD207. The results demonstrated that L. crispatus could strongly upregulate the expression levels of Langerin/CD207, accompany with much higher endocytic activity and Th1 cytokines production. These results indicated that L. crispatus could induce THP-1 differentiate into functional LC which can prevent HIV-1 infection and dissemination in vivo through Langerin/CD207 and immune regulation. As a result, vaginal lactobacilli can serve as delivery systems of mucosal immune vaccine for further research. On this basis, we compared the effect of other 5 strains of lactobacilli on THP-1, finding that there were differences in affecting morphology, 5 kind of CLR expression, DC associated molecules and phagocytosis. These results indicate there is a need of further evaluation and screening to conclude whether the different lactobacilli are qualified candidate strains as vaccine delivery systems. In conclusion, the present study screened the lactobacilli strains which could upregulate Langerin/CD207 expression and immune regulation function on THP-1. The research established the basis for evaluating the vaginal delivery systems and further concentration on monocytes. Meanwhile it was helpful to establish appropriate evaluation system in vitro according to the mechanism of resistance to HIV infection. So we can prodetermine the effect of delivery systems alone on HIV-1infection and dissemination. |
| 语种 | 中文 |
| 公开日期 | 2013-04-23 |
| 内容类型 | 学位论文 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7371]  |
| 专题 | 昆明动物研究所_分子免疫生物学 |
| 推荐引用方式 GB/T 7714 | 郎丰超. 女性生殖道共生菌诱导Langerhans细胞特异性C型凝集素受体Langerin（CD207）表达的研究[D]. 北京. 中国科学院研究生院. 2011. |
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