Molecular Patterns of Borrelia - Chemical Structure and Innate Immune Responses involving LPS Binding Protein (LBP)

疏螺旋体的分子模式 - 涉及 LPS 结合蛋白 (LBP) 的化学结构和先天免疫反应

• 批准号: 5357987
• 负责人: Privatdozent Dr. Nicolas Schröder
• 金额: --
• 依托单位: Institut für Pathologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5357987?language=en
• 关键词: Molecular; Patterns; Borrelia; Chemical; Structure

The object of this study is to define the molecular mechanisms of the induction of innate immune responses induced by glycolipids isolated from the outer membrane of spirochetes including Treponema, Borrelia and Leptospira. Following chemical characterization, we will perform structure-function analysis of cellular host responses via Toll-like receptors (TLRs). Defining structural elements of spirochetal glycolipids required for biological activity should lead to the definition of molecular patterns of bacterial compounds essential for stimulation of innate immune responses in general. In previous work, we isolated glycolipids of the outer membrane of two treponeme strains, and chemical analysis revealed a structure closely related to Lipoteichoic acid (LTA) of Gram-positive bacteria. These compounds induced cytokine release in mono- nuclear cells depending on Lipopolysccharide (LPS) binding protein (LBP), CD14 and TLRs. Based on these findings, the proposed project extends this work to clinically highly relevant spirochetes including B. burgdorferi. Chemical analysis will be performed in close collaboration with the Borstel Research Center followed by stimulation experiments using cell lines transfected with different TLRs established in our lab. This will be completed by studies on TLR-deficient mice, and clinical investigations on the role of TLR-polymorphisms in Lyme disease. Defining the molecular patterns required for innate immune responses may aid in developing novel prevention and intervention strategies in infectious caused by spirochetes and other bacteria.

本研究的目的是确定从螺旋体包括密螺旋体、疏螺旋体和钩端螺旋体的外膜分离的糖脂诱导的先天免疫应答的分子机制。在化学表征之后，我们将通过Toll样受体（TLR）对细胞宿主反应进行结构-功能分析。定义螺旋体糖脂的生物活性所需的结构要素，应导致定义的分子模式的细菌化合物的刺激先天免疫反应的一般。在先前的工作中，我们分离了两种密螺旋体菌株的外膜糖脂，化学分析揭示了与革兰氏阳性菌的脂磷壁酸（LTA）密切相关的结构。这些化合物依赖于脂多糖（LPS）结合蛋白（LBP）、CD 14和TLR在单核细胞中诱导细胞因子释放。基于这些发现，拟议的项目将这项工作扩展到临床高度相关的螺旋体，包括B。burgdorferi。将与Borstel研究中心密切合作进行化学分析，然后使用我们实验室建立的不同TLR转染的细胞系进行刺激实验。这将通过对TLR缺陷小鼠的研究和对TLR多态性在莱姆病中的作用的临床研究来完成。确定先天免疫应答所需的分子模式可能有助于开发新的预防和干预策略，以预防螺旋体和其他细菌引起的感染。