Evolutionary and functional relationships of cytokines expressed by the helminth Echinococcus multilocularis and its mammalian host

多房棘球绦虫及其哺乳动物宿主表达的细胞因子的进化和功能关系

• 批准号: 180451182
• 负责人: Professor Dr. Klaus Brehm
• 金额: --
• 依托单位: Institut für Hygiene und Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/180451182?language=en
• 关键词: Evolutionary; functional; relationships; cytokines; expressed

Parasitic helminths induce long-lasting, chronic infections associated with Th2-biased immune responses and strong immunosuppressive effects, elicited by regulatory T cells and alternatively activated macrophages through the secretion of cytokines like IL-10 and TGF-β. As metazoans, helminths are closely related to their mammalian hosts and utilize evolutionary conserved cytokines for cell-cell-communication that are also involved in regulating innate and adaptive immune responses in mammals. The present project investigates whether parasitic helminths utilize evolutionary conserved cytokines to interfere with the anti-parasitic immune response and to alter host cell physiology at the site of infection. As a model, we use the larval stage of the tapeworm Echinococcus multilocularis for which we have developed sophisticated in vitro cultivation systems, initiated a genome sequencing project, and characterized several evolutionary conserved cytokines, in particular of the TGF-β/BMP-family. This project first aims to functionally express the parasite’s TGF-β/BMP-orthologs in mammalian expression systems and to study their interaction with corresponding surface receptors of the TGF-β/BMP-receptor families of the host. Based on the identified activation patterns, in vitro assays to study the effects of parasite-derived cytokines from early and late stages of the infection on the activation of immune-effector cells and cells of the liver, the primary site of infection, will be established.

寄生蠕虫诱导与Th 2偏向的免疫应答和强免疫抑制作用相关的持久慢性感染，所述免疫应答和强免疫抑制作用由调节性T细胞和交替活化的巨噬细胞通过分泌细胞因子如IL-10和TGF-β引起。作为后生动物，蠕虫与其哺乳动物宿主密切相关，并利用进化上保守的细胞因子进行细胞间通讯，这些细胞因子也参与调节哺乳动物的先天性和适应性免疫应答。本项目研究寄生蠕虫是否利用进化保守的细胞因子来干扰抗寄生虫免疫反应并改变感染部位的宿主细胞生理学。作为一个模型，我们使用绦虫的幼虫阶段的多房棘球绦虫，我们已经开发了复杂的体外培养系统，启动了基因组测序计划，并表征了几个进化保守的细胞因子，特别是TGF-β/BMP家族。本项目的第一个目标是在哺乳动物表达系统中功能性表达疟原虫的TGF-β/BMP-直系同源物，并研究它们与宿主TGF-β/BMP-受体家族的相应表面受体的相互作用。基于所鉴定的活化模式，将建立体外测定以研究来自感染的早期和晚期阶段的寄生虫衍生的细胞因子对免疫效应细胞和肝脏（感染的主要部位）细胞的活化的影响。