Toll样受体调节Th17细胞致梅毒血清固定作用的队列研究

Although syphilis can be effectively treated by penicillin, the state of serofast becomes more and more common. Syphilis serofast not only causes serious psychological and mental problems, but also largely increases the risk of neurosyphilis. However, the formation mechanism of serofast is far from clear. The applicant’s previous studies have primarily explored the associations between syphilis serofast and cellular immunity, and have identified the significance of T helper cell 17(Th17) in syphilis serofast. Based on these results, this study aims to furtherly explore the associations among human toll-like receptors (TLRs), Th17 and syphilis serofast, with a research thinking of ‘TLRs- cytokine-Th17-serofast’ pathway. To achieve this goal, a cohort study among syphilis infected patients and a case-control study among syphilis serofast group, serological cure group, and healthy people group will be established. The expression levels of TLRs and TLRs mRNA, Th17 and the secreted cytokines (IL-17 and RORγt), the cytokines in the ‘TLRs- cytokine-Th17’ pathway (IL-6, IL-23 and STAT3) will be measured and compared among three study groups and among different observed time. The role of TLRs and Th17 in the formation of syphilis serofast will be fully elucidated based on the analysis results. The potential mechanisms by which TLRs regulate Th17 are constructed by the pathways of TLR4-IL6-Th17, TLR2/TLR4-IL23-Th17 and TLR3-STAT3-Th17. Finally, this study will comprehensively explain the formation mechanism of syphilis serofast from both population perspective and molecular biology perspective. The research results will not only provide a new theory for the interpretation of syphilis serofast, but also a new idea for syphilis treatment in cellular immune intervention. The information sourcing from this study will benefit largely for the precise prevention and treatment of syphilis.

尽管青霉素能有效治疗梅毒，但梅毒血清固定的情况越来越普遍，不仅造成患者心理和精神的严重损害，也大大增加了神经梅毒发生的风险。然而，血清固定的形成机制远未阐明。申请者前期已初步探讨了血清固定与细胞免疫的关系。基于此，本研究以Toll样受体（TLRs）为切入点，以主要识别梅毒螺旋体的TLR2和TLR4为代表，以Th17细胞为中间纽带，建立“TLRs-细胞因子-Th17-血清固定”的研究路径，通过梅毒患者队列研究和构建血清固定组、血清治愈组和健康对照组的病例对照研究，阐明TLRs及Th17在梅毒血清固定形成过程中的作用及TLRs调控Th17的潜在机制。本研究从人群水平和分子生物学水平综合阐释梅毒血清固定的形成机制，研究结果将为梅毒血清固定的疾病解释提供新理论，为梅毒防控在细胞免疫干预方面提供新思路，对梅毒的精准预防和治疗具有较强的实际指导意义。

梅毒血清固定现象越来越普遍，不仅给患者的心理及精神造成严重影响，也大大增加了神经梅毒的发生风险。然而，梅毒血清固定的形成机制远未阐明。本项目建立完善了梅毒患者随访队列，构建了梅毒血清固定组、梅毒血清治愈组和健康对照组的病例对照研究，从人群水平和分子生物学水平综合分析梅毒血清固定的形成机制。项目研究分析了梅毒患者血清滴度分布特征，阐明了梅毒血清固定患者血清滴度转归规律 ，探索了影响梅毒血清固定和血清治愈的风险因素，揭示了梅毒血清固定与神经梅毒的密切关系。以Toll样受体（TLRs）-细胞因子-Th17细胞-血清固定的研究路径，分析了梅毒血清固定组、梅毒血清治愈组和健康对照组在细胞免疫功能、Th17细胞及相关细胞因子表达、调节性T细胞及相关细胞因子表达和TLRs mRNA表达具有显著差异，揭示了TLR受体、相关细胞因子和Th17细胞等表达情况与梅毒血清固定形成的关系。研究结果为梅毒血清固定的疾病解释提供了新理论，对梅毒的精准预防和治疗具有重要指导意义。