Characterization of the determinants of snail-schistosome compatibility

蜗牛-血吸虫相容性决定因素的表征

• 批准号: RGPIN-2018-05209
• 负责人: Hanington, Patrick
• 金额: $ 3.64万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=713541
• 关键词: Characterization; determinants; snail; schistosome; compatibility

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.

血吸虫病是一种由血吸虫属的寄生扁虫引起的疾病。全世界有2.6亿多人受其折磨，因这种疾病而丧失的残疾调整寿命年数与疟疾不相上下。作为其生命周期的一部分，寄生虫必须在特定种类的蜗牛中进行其幼虫发育。蜗牛作为中间宿主几乎每一个~ 18，000不同种类的寄生虫扁形虫，和他们的重要性，寄生虫的成功是突出的事实，一个兼容的蜗牛宿主的存在往往定义吸虫病的地理分布，如血吸虫病。有很大的兴趣在推进我们的理解是什么使一个蜗牛兼容与特定的寄生扁形虫物种，另一个不兼容。曼氏血吸虫（Schistosoma mansoni）可引起人类肠道血吸虫病，它与一种与之相容的蜗牛宿主物种光滑双脐螺（Biomphalaria glabrata）一起沿着出现，作为研究蜗牛-双脐螺相容性决定因素的模型。对该模型的研究已经确定了与B相关的体液和细胞因子。glabrata免疫应答作为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。 我们的研究集中在表征B的细胞和体液成分的界面。glabrata幼虫攻击时的免疫应答。mansoni蜗牛免疫细胞包裹寄生虫对于消除感染至关重要。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，并使这些细胞启动适当的免疫效应子来杀死寄生虫。我们过去的工作通过描述蜗牛中的第一个细胞生长因子，并证明由该生长因子刺激发育的细胞更适合杀死S。mansoni现在，由于这项工作，我们对B体内发生的免疫过程有了更深入的了解。光滑的我们也有试剂和生物测定法，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特点的B。glabrata对S.我们通过解决两个具体目标来应对曼索尼挑战，我们已经确定这两个目标是蜗牛成功清除寄生虫的核心，并建立在我们过去NSERC DG支持的工作基础上： 1.表征B的过程。glabrata血细胞发育和建立特定的血细胞亚群在细胞介导的抗溶酶体免疫应答过程中的作用。 2.探讨血细胞产生的循环体液免疫因子促进细胞介导的对寄生虫幼虫的杀伤。