Immune evasion by the human blood fluke Schistosoma man*

人类血吸虫血吸虫人的免疫逃避*

• 批准号: 6732765
• 负责人: Philip T LoVerde
• 金额: $ 4.03万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6732765
• 关键词: SCID mouse; SDS polyacrylamide gel electrophoresis; Schistosoma mansoni; active immunization; binding sites; biological signal transduction; complement; genetic regulation; host organism interaction; immunology; laboratory rabbit; laboratory rat; ligands; parasite infection mechanism; passive immunization; phosphorylation; protein protein interaction; protein purification; recombinant proteins; schistosomiasis; serine threonine protein kinase; tissue /cell culture; transforming growth factors; western blottings; yeast two hybrid system

DESCRIPTION (provided by applicant) This research will be done primarily in Israel at Tel Aviv University in collaboration with Drs. Zvi Fishelson and Daniel Gold as an extension of NIH grant # R01AI46762. The blood fluke Schistosoma mansoni causes intestinal schistosomiasis, a parasitic disease affecting the lives of millions throughout Africa and South America. Young and adult worms of S. mansoni express on their surface several types of immune evasion molecules which protect them for at least 10 years within infected patients. SCIP-1 (Schistosome Complement Inhibitory Protein type 1) is a 94kDa protein functionally related to the human complement inhibitor CD59. A role for SCIP-1 has been postulated in the ability of the schistosome parasite to resist the effects of the complement membrane attack complex. The major aims of this proposed research are: a. to elucidate the interaction of SCIP-1 with components of the complement system, and b. to demonstrate the effect of SCIP-1 in cell culture and animal models. Data suggests that SCIP-1 is paramyosin (Pmy), an invertebrate muscular protein, and that it specifically binds to the C9 component of complement. The sites in SCIP-1/Pmy and C9 involved in their binding will be identified and the surface location of SCIP-1/Pmy on the larvae and worms will be analysed. Native and recombinant SCIP-1/Pmy will be transplanted into surrogate CD59-negative cells to study its effect on complement. Additionally, the protective efficacy of SCIP-1/Pmy will be evaluated in a mouse model of infection by passive and active immunization. This proposed research will contribute to our understanding of the immune evasion mechanisms of S. mansoni and to development of an immunotherapeutical approach against schistosomiasis.

描述（由申请人提供） 这项研究将主要在特拉维夫大学与DRS合作在以色列进行。 Zvi Fishelson和Daniel Gold作为NIH赠款＃R01AI46762的扩展。 曼森的血液血吸虫可引起肠道血吸虫病，这是一种寄生疾病，影响了整个非洲和南美数百万的生活。 S. Mansoni的年轻和成人蠕虫表面表达了几种类型的免疫逃避分子，这些分子在感染患者中至少保护了10年。 SCIP-1（血吸虫补体抑制蛋白1型）是与人补体抑制剂CD59功能相关的94KDA蛋白。 SCIP-1的角色已在黑素寄生虫抵抗补体膜攻击复合物的作用的能力中。这项拟议研究的主要目的是：阐明SCIP-1与补体系统组件的相互作用，b。证明SCIP-1在细胞培养和动物模型中的影响。数据表明SCIP-1是无脊椎动物肌肉蛋白的帕果素（PMY），并且它专门结合了补体的C9成分。将确定SCIP-1/PMY和C9中的位点，并将分析SCIP-1/PMY在幼虫和蠕虫上的表面位置。天然和重组SCIP-1/PMY将被移植到替代CD59阴性细胞中，以研究其对补体的影响。另外，将通过被动和主动免疫在小鼠感染模型中评估SCIP-1/PMY的保护效果。这项提出的研究将有助于我们理解曼氏链球菌的免疫逃避机制，并开发针对血吸虫病的免疫治疗方法。