Involvement of dendritic cell Toll-like receptors in the innate response to Litomosoides sigmodontis infection and deviation by their Wolbachia endobacteria

树突状细胞 Toll 样受体参与对 Litomosoides sigmodontis 感染的先天反应及其沃尔巴克氏体内生细菌的偏差

• 批准号: 5449987
• 负责人: Professor Dr. Achim Hoerauf
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie, Immunologie und Parasitologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5449987?language=en
• 关键词: Involvement; dendritic; cell; Toll; like

Filarial worm infections result in a mixed Th1/Th2 pro-inflammatory or a T regulatory (Tr-1) anti-inflammatory immune response, rather than the typical Th2 response seen to other worm infections. Confounding our understanding of the immune mechanisms is the presence of Wolbachia endosymbiotic bacteria in filariae, a second organism for stimulating the immune response. This laboratory has demonstrated that Wolbachia are sources of Toll-like receptor (TLR) 2 and 4 ligands. We have also shown that a ency in TLR4 leads to increased permissiveness to infection by the rodent filaria Litomosoides sigmodontis. A role for TLR is further suggested by our preliminary results with MyD88-/- mice, which have higher worm loads. Other preliminary results suggest dendritic cells (DC) are important for the innate response which controls filarial establishing. We aim to characterize how DC detect worms through TLR and to define the role of Wolbachia in the immune response by answering the following questions. What are the effects of TLR2, TLR4 and MyD88? How do filarial antigens affect the innate immune response through DC via TLR? Which organism (nematode, Wolbachia, or both) is the source of TLR antigen(s) which stimulate DC? The study would provide novel data on how innate responses via DC and TLR are induced against helminths, important knowledge for ultimate vaccine design.

丝虫感染导致混合的Th 1/Th 2促炎或T调节（Tr-1）抗炎免疫应答，而不是对其他蠕虫感染所见的典型Th 2应答。混淆我们对免疫机制的理解是在丝虫中存在Wolbachia内共生细菌，这是刺激免疫反应的第二种生物。该实验室已经证明Wolbachia是Toll样受体（TLR）2和4配体的来源。我们还表明，TLR 4的表达增加了啮齿类动物丝状虫感染的容许性。我们对MyD 88-/-小鼠的初步结果进一步表明TLR的作用，MyD 88-/-小鼠具有较高的蠕虫负荷。其他初步结果表明树突状细胞（DC）是重要的先天反应，控制丝虫建立。我们的目标是表征DC如何通过TLR检测蠕虫，并通过回答以下问题来定义Wolbachia在免疫应答中的作用。TLR 2、TLR 4和MyD 88的作用是什么？丝虫抗原如何通过TLR通过DC影响先天免疫应答？哪种生物（线虫、沃尔巴克氏体或两者）是刺激DC的TLR抗原的来源？该研究将提供关于如何通过DC和TLR诱导针对蠕虫的先天反应的新数据，这是最终疫苗设计的重要知识。