Characterization of the determinants of snail-schistosome compatibility

血吸虫病是一种由血吸虫属的寄生扁虫引起的疾病。它折磨着全世界2.6亿多人，因这种疾病失去的残疾调整生命年可与疟疾相媲美。作为其生命周期的一部分，血吸虫必须在一种特定的蜗牛体内进行幼虫发育。蜗牛几乎是18,000种不同的扁虫寄生虫的中间寄主，它们对寄生虫成功的重要性被这样一个事实所突出：一个相容性的蜗牛寄主的存在通常定义了血吸虫病等吸虫疾病的地理分布。我们很有兴趣进一步了解是什么使一种蜗牛与一种特定的寄生扁形虫相容，而另一种又不相容。引起人类肠道血吸虫病的曼氏血吸虫（Schistosoma mansoni）与与之相容的一种蜗牛寄主光螺（Biomphalaria glabrata）一起出现，作为研究蜗牛-血吸虫相容性决定因素的模型。该模型的研究已经确定了与光斑双胞杆菌免疫反应相关的体液和细胞因素是感染结果的关键决定因素，与宿主和寄生虫遗传学/表观遗传学、蛋白质组学/转录组学调节和环境因素协同作用。******我们的研究主要集中在表征幼虫曼氏梭菌攻击期间光斑拟虫免疫反应的细胞和体液元素的界面。蜗牛免疫细胞对寄生虫的包封是消除感染的关键。因此，蜗牛必须保持足够的免疫细胞群，能够将这些细胞招募到寄生虫表面，并让这些细胞启动适当的免疫效应物来杀死寄生虫。我们过去的工作涉及到成功反应的每一个要素，通过描述蜗牛体内的第一个细胞生长因子，并证明受该生长因子刺激而发育的细胞更适合杀死S. mansoni。现在，由于这项工作，我们对发生在B. glabrata体内的免疫过程有了更深入的了解。我们也有试剂和生物测定，使我们能够用机械透镜研究蜗牛的免疫过程。我们建议继续我们的工作，通过解决两个特定的目标，我们已经确定了蜗牛成功清除寄生虫的核心，并建立在我们过去的NSERC dg支持的工作：******1。目的：表征光裂裂螨血细胞发育的过程，并确定特定血细胞亚群在细胞介导的抗血吸虫免疫反应中的作用。******目的：探讨血细胞产生的循环体液免疫因子促进细胞介导的寄生虫幼虫的杀伤。

Schistosomiasis is a disease caused by parasitic flatworms of the genus Schistosoma. It afflicts over 260 million people worldwide, and the disability-adjusted life years lost to this disease rival that of malaria. As a part of their life cycle, schistosomes must undertake their larval development within a specific species of snail. Snails serve as the intermediate host for almost every one of the ~18,000 different species of parasite flatworm, and their importance to the success of the parasite is highlighted by the fact that the presence of a compatible snail host often defines the geographical distribution of trematode diseases like schistosomiasis. There is a great deal of interest in advancing our understanding of what makes one snail compatible with a particular parasitic flatworm species, and another incompatible. Schistosoma mansoni, which causes intestinal schistosomiasis in humans, has emerged along with one of its compatible snail host species, Biomphalaria glabrata, as a model for studying the determinants of snail-schistosome compatibility. Studies of this model have identified humoral and cellular factors associated with the B. glabrata immune response as key determinants of infection outcomes, acting in concert with host and parasite genetics/epigenetics, proteomic/transcriptomic regulation and environmental factors.******Our investigations have focused on characterizing the interface of the cellular and humoral elements of the B. glabrata immune response during challenge by larval S. mansoni. Encapsulation of the parasite by snail immune cells is critical for elimination of the infection. Thus, it is essential for snails to maintain sufficient immune cell populations, to be able to recruit those cells to the parasite surface and have those cells initiate the proper immune effectors to kill the parasite. Our past work touched on each of these elements of a successful response by characterizing the first cellular growth factor in a snail and demonstrating that the cells that develop from stimulation by that growth factor are better suited for killing of S. mansoni. Now, because of this work, we have greater insight into the immune processes taking place within B. glabrata. We also have reagents and bioassays that allow us to investigate snail immune processes with a mechanistic lens. We propose to continue our work characterizing the B. glabrata immune response to S. mansoni challenge by addressing two specific objectives that we have identified as being central to successful parasite clearance by the snail and that build upon our past NSERC DG-supported work:******1. To characterize the process of B. glabrata haemocyte development and to establish the role of specific haemocyte subsets during the cell-mediated anti-schistosome immune response.******2. To investigate the circulating humoral immune factors produced by haemocytes facilitating cell-mediated killing of the larval parasite.