BIOLOGY OF TREMATODE-SNAIL ASSOCIATIONS

吸虫-蜗牛协会的生物学

• 批准号: 6697469
• 负责人: ERIC SAMUEL LOKER
• 金额: $ 25.26万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6697469
• 关键词: Cestoda; Gastropoda; Schistosoma mansoni; Trematoda; affinity chromatography; fluorescent in situ hybridization; hemolymph; host organism interaction; immunoprecipitation; immunosuppression; intracellular parasitism; larva; lectin; membrane activity; microorganism immunology; molecular cloning; parasitic diseases; polymerase chain reaction; protein structure; secretory protein; tissue /cell culture

Schistosomes and other snail-transmitted parasites persist as significant public health problems, particularly in children and women, across much of the developing world. The use by these parasites of freshwater snails as intermediate hosts makes control very difficult. We need to develop a broader base of knowledge regarding these parasites, particularly in light of recent concerns about the potential evolution among schistosomes of resistance to praziquantel. This proposal focuses on the interactions between two trematodes, Schistosoma mansoni and Echinostoma paraensei, and their molluscan host Biomphalaria glabrata, with the goal of obtaining a deeper understanding of how these parasites establish infections in snails, and more importantly, how the snail can overcome these infections. Capitalizing on discoveries made during our previous funding period, we intend to further characterize the structure, diversity and genomic organization of members of a family of B. glabrata blood proteins termed fibrinogen-related proteins or FREPs, that have several attributes that make them likely candidates as non-self recognition molecules in B. glabrata. As such, they may be key regulators of the molluscan response to trematode infection and become particularly useful in future attempts to develop transgenic snails resistant to schistosome infection. Because FREPs exist in a multigene family and are invertebrate members of the immunoglobulin superfamily, they also provide a unique model to study the evolution of invertebrate immune responses. Also outlined are experiments to characterize the molecules used by trematode larvae in affecting host defense cells (hemocytes) and to identify hemocyte molecules that are targeted for attack. Finally, we propose to examine a model system in which snails can be provoked to develop acquired resistance to trematode infection. We will apply the tools and insights developed in recent years to this model to reveal the factors most closely linked to the resistant state. These studies will provide novel insights pertaining to both basic and applied aspects of schistosome (trematode) biology.

血块和其他蜗牛传播的寄生虫仍然存在着重要的公共卫生问题，尤其是在整个发展中国家的儿童和妇女中。 这些寄生虫用作中间宿主的用途使控制非常困难。 我们需要建立关于这些寄生虫的更广泛的知识基础，特别是考虑到最近对抗Praziquantel耐药性的潜在进化的担忧。 该提案的重点是两种trematodes曼氏菌和eChinostoma paraensei的相互作用，以及他们的软体动物宿主寄生的biomphalararia glabrata，目的是对这些寄生虫在蜗牛中如何建立感染方式，以及如何更重要的是，如何克服这些感染。利用在我们上一期的资金期间发现的发现，我们打算进一步描述glabrata血蛋白家族成员的结构，多样性和基因组组织，称为纤维蛋白原相关的蛋白质或FREP，这些蛋白质或FREP具有多种属性，这些属性可能使它们成为B. glabrata中非自我识别分子的几种属性。 因此，它们可能是软体动物对Trematode感染反应的关键调节剂，并在未来开发抗螺旋体感染具有抗性的转基因蜗牛的尝试中变得尤为有用。 由于FREP存在于多基因家族中，并且是免疫球蛋白超家族的无脊椎动物成员，因此它们还提供了一个独特的模型来研究无脊椎动物免疫反应的演变。 还概述了trematode幼虫在影响宿主防御细胞（血细胞）中使用的分子的实验，并确定针对攻击的血细胞分子。 最后，我们建议检查一个模型系统，在该模型系统中，可以引起蜗牛以发展出对Trematode感染的获得性抗性。 近年来，我们将把工具和见解应用于该模型，以揭示与抵抗状态最紧密联系的因素。 这些研究将提供与血块（Trematode）生物学基本和应用方面有关的新见解。