Immune evasion by the human blood fluke Schistosoma man*

描述(由申请人提供) 这项研究将主要在以色列特拉维夫大学与Zvi Fishelson博士和Daniel Gold博士合作完成，作为NIH#R01AI46762号补助金的延伸。 曼氏血吸虫引起肠道血吸虫病，这是一种影响非洲和南美洲数百万人生活的寄生虫病。曼氏沙门氏菌的幼虫和成虫在其表面表达几种类型的免疫逃避分子，这些分子在感染的患者体内保护它们至少10年。SCIP-1(血吸虫补体抑制蛋白1)是一种与人类补体抑制因子CD59功能相关的94 kDa蛋白。SCIP-1在血吸虫抵抗补体膜攻击复合体的能力中起着重要作用。本研究的主要目的是：1.阐明SCIP-1与补体系统成分的相互作用；2.阐明SCIP-1在细胞培养和动物模型中的作用。数据表明，SCIP-1是副肌球蛋白(Pmy)，是一种无脊椎动物肌肉蛋白，它与补体的C9成分特异结合。将确定SCIP-1/Pmy和C9中与其结合的位点，并分析SCIP-1/Pmy在幼虫和蠕虫上的表面位置。将天然的和重组的SCIP-1/PMY移植到CD59阴性的代理细胞中，研究其对补体的影响。此外，将在被动和主动免疫的小鼠感染模型中评估SCIP-1/Pmy的保护效果。这项研究将有助于我们了解曼氏血吸虫的免疫逃避机制，并有助于开发针对血吸虫病的免疫治疗方法。

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.