CUTANEOUS IMMUNE RESPONSE IN LYME DISEASE AND SECONDARY SYPHILIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。性病梅毒是一种慢性炎症性疾病，由其病原体梅毒螺旋体的持续存在引起。虽然局部梅毒螺旋体感染部位的免疫/炎症反应最终可能不利于保护性免疫和临床表现的发展，但这些局部细胞过程尚未用现代细胞和分子免疫学工具在人类身上表征。导致这些潜在有害炎症过程的梅毒螺旋体成分也仍然没有得到很好的描述。我们目前对梅毒和HIV感染之间相互作用的了解有限，这进一步损害了我们对梅毒细胞免疫的理解。因此，这项拟议的研究有三个具体目标。在具体目标1中，我们将对皮肤活检组织进行免疫细胞化学分析，并对吸引水泡中的白细胞进行流式细胞仪分析，以表征HIV阳性和HIV+二期梅毒患者的皮肤细胞免疫过程。这些研究的数据将与我们的体外研究相关，该研究涉及梅毒螺旋体和梅毒螺旋体脂蛋白激活免疫效应细胞。在具体目标2中，我们将使用相同的免疫细胞化学和流式细胞术方法来表征对合成的梅毒螺旋体脂蛋白类似物(脂肽)的皮肤炎症反应。这些实验是我们假设梅毒螺旋体脂蛋白是梅毒感染期间的主要炎症介质的结果。在我们观察到梅毒螺旋体脂蛋白类似物在体外诱导HIV基因表达的基础上，特定目标3的实验将阐明这一现象背后的机制。这项研究的一个主要长期目标是阐明梅毒感染过程中产生临床表现和保护性免疫的免疫/炎症事件。一个同样重要的目标是获得细胞和分子数据，这些数据将补充我们对梅毒和艾滋病毒感染之间相互作用的新理解，包括梅毒可能成为艾滋病毒传播的辅助因素，以及艾滋病毒感染改变梅毒的临床进程。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Venereal syphilis is a chronic inflammatory disorder driven by the persistence of its etiologic agent Treponema pallidum. Though the immune/inflammatory response at sites of local treponemal infection may ultimately underly the development of both protective immunity and clinical manifestations, these local cellular processes have yet to be characterized in humans using the tools of contemporary cellular and molecular immunology. The components of T. pallidum that induce these potentially deleterious inflammatory processes also remain poorly characterized. Our understanding of cellular immunity in syphilis is further compromised by our currently limited knowledge concerning the interactions between syphilis and HIV infection. Accordingly, the proposed research has three Specific Aims. In Specific Aim 1, we will perform immunocytochemical analysis of skin biopsies and flow cytometry analysis of leukocytes in suction blisters to characterize cutaneous cellular immune processes in HIV- and HIV+ patients with secondary syphilis. Data from these studies will be correlated with our in vitro research involving immune effector cell activation by T. pallidum and treponemal lipoproteins. In Specific Aim 2, we will use the same immunocytochemical and flow cytometric approaches to characterize the cutaneous inflammatory response to synthetic analogs (lipopeptides) of T. pallidum lipoproteins. These experiments are an outgrowth of our hypothesis that T. pallidum lipoproteins are major inflammatory mediators during syphilitic infection. Building upon our observation that T. pallidum lipoprotein analogs induce HIV gene expression in vitro, the experiments in Specific Aim 3 will elucidate the mechanisms which underly this phenomenon. A principal long-term objective of this research is to elucidate the immune/inflammatory events during syphilitic infection which engender both clinical manifestations and protective immunity. An equally important objective is to obtain cellular and molecular data which will complement our emerging understanding of the interactions between syphilis and HIV infection, including the potential for syphilis to serve as a co-factor for HIV transmission and for HIV infection to alter the clinical course of syphilis.