CUTANEOUS IMMUNE RESPONSE IN LYME DISEASE AND SECONDARY SYPHILIS

莱姆病和二期梅毒的皮肤免疫反应

• 批准号: 7719087
• 负责人: Justin D Radolf
• 金额: $ 2.62万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719087
• 关键词: Biopsy; Bulla; Cell physiology; Cellular Immunity; Chronic; Clinical; Complement; Computer Retrieval of Information on Scientific Projects Database; Cutaneous; Data; Development; Disease; Effector Cell; Event; Flow Cytometry; Funding; Gene Expression; Grant; HIV; Human; Immune; Immune response; Immunity; In Vitro; Infection; Inflammatory; Inflammatory Response; Institution; Knowledge; Leukocytes; Lipoproteins; Lyme Disease; Mediator of activation protein; Molecular; Molecular Immunology; Patients; Process; Research; Research Personnel; Resources; Site; Skin; Source; Suction; Syphilis; Treponema pallidum; Treponemal Infections; United States National Institutes of Health; Virus Diseases; analog; research study; tool; transmission process

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 underlie 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 human immunodeficiency virus (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 underlie 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 性病梅毒是一种慢性炎症性疾病驱动的持久性病原体梅毒螺旋体。虽然局部密螺旋体感染部位的免疫/炎症反应可能最终成为保护性免疫和临床表现的基础，但这些局部细胞过程尚未在人类中使用当代细胞和分子免疫学的工具进行表征。T.引起这些潜在有害的炎症过程的苍白球的特征也仍然很差。我们对梅毒细胞免疫的理解进一步受到我们目前关于梅毒和人类免疫缺陷病毒（HIV）感染之间相互作用的有限知识的影响。因此，本研究有三个具体目标。在具体目标1中，我们将对皮肤活检进行免疫细胞化学分析，并对抽吸水泡中的白细胞进行流式细胞术分析，以表征二期梅毒HIV-和HIV+患者的皮肤细胞免疫过程。来自这些研究的数据将与我们的体外研究相关，该研究涉及T。梅毒和密螺旋体脂蛋白。在特定目标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T合成类似物（脂肽）的皮肤炎症反应。苍白球脂蛋白这些实验是我们假设T。梅毒脂蛋白是梅毒感染过程中的主要炎症介质。根据我们的观察，T。苍白球脂蛋白类似物在体外诱导HIV基因表达，具体目标3中的实验将阐明这一现象的机制。 本研究的一个主要长期目标是阐明梅毒感染过程中的免疫/炎症事件，这些事件产生临床表现和保护性免疫。同样重要的目标是获得细胞和分子数据，这将补充我们对梅毒和HIV感染之间相互作用的新认识，包括梅毒作为HIV传播的辅助因素和HIV感染改变梅毒临床过程的可能性。