Proteomic approach to characterisation of pathogenesis mechanisms in fasciolosis

蛋白质组学方法表征片形吸虫病的发病机制

• 批准号: 250074-2006
• 负责人: Spithill, Terry
• 金额: $ 4.07万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2006
• 资助国家: 加拿大
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=340425
• 关键词: Proteomic; approach; characterisation; pathogenesis; mechanisms

Liver fluke disease is due to infection of sheep and cattle by the parasites Fasciola hepatica and F. gigantica (tropical liver fluke). This infection causes economic losses of over $3b p.a., to the agricultural sector in Africa, Asia, S and N America, and Europe with over 500m animals infected. The parasite is transmitted by ingestion of infective cysts from eating contaminated plants or water.  The parasites invade the liver and cause haemorrhagic lesions and anaemia. We aim to assist the development of an effective vaccine or drug for control of Fasciola by identifying host and parasite factors considered important in infection. We are applying a new approach, using a technique termed "biomarker profiling", to identify factors in serum of infected animals that are biomarkers of disease. These biomarkers are indicators of both the animal's response to infection as well as parasite factors released into the animal. By identifying these biomarkers, we aim to understand how the parasite manipulates the host to establish infection; we also aim to develop better diagnostic tests for the disease. A feature of liver fluke disease is that F. hepatica and F. gigantica differ in virulence in animals; sheep acquire resistance to F. gigantica but not F. hepatica suggesting that these two parasites differ in some key trait(s) which renders F. gigantica more susceptible to the host's immune system. We aim to understand this difference in behaviour by also studying the biomarker profiles of the two parasites: biomarkers that differ in expression represent virulence factors that are prime targets for drug/vaccine therapy. This work is important to primary producers world wide, including subsistence farmers in Africa and Asia where large animals are the major source of household income, savings and food supply. The knowledge gained here will make us better informed on how to control this disease and related diseases, such as schistosomiasis, and has benefits for Canada in terms of (i) understanding how parasites infect cattle and sheep; (ii) new patentable products; (iii) better diagnostic tests; (iv) training of high quality students; (v) demonstrating leadership in assisting developing countries to become self sustaining in terms of food production.

肝吸虫病是由于羊和牛感染寄生虫肝片吸虫和F。热带肝吸虫（Tropical liver fluke）这种感染每年造成超过30亿美元的经济损失，非洲、亚洲、南北美洲和欧洲的农业部门感染了5亿多只动物。这种寄生虫通过进食受污染的植物或水而摄入感染性包囊传播。寄生虫侵入肝脏，引起出血性病变和贫血。我们的目标是协助开发一种有效的疫苗或药物，通过确定宿主和寄生虫因素被认为是重要的感染控制片形吸虫。我们正在应用一种新的方法，使用一种称为“生物标志物分析”的技术，以确定感染动物血清中作为疾病生物标志物的因子。这些生物标志物是动物对感染的反应以及释放到动物体内的寄生虫因子的指标。通过识别这些生物标志物，我们的目标是了解寄生虫如何操纵宿主建立感染;我们还旨在开发更好的疾病诊断测试。肝吸虫病的一个特点是F。hepatica和F.在动物中，沙门氏菌的毒力不同;绵羊获得了对沙门氏菌的抗性。而不是F. hepatica表明这两种寄生虫在一些关键性状上存在差异，这使得F.寄生虫更容易受到宿主免疫系统的影响。我们的目标是通过研究这两种寄生虫的生物标志物谱来了解这种行为差异：表达不同的生物标志物代表毒力因子，这些毒力因子是药物/疫苗治疗的主要目标。这项工作对全世界的初级生产者，包括非洲和亚洲的自给农民都很重要，在这些地区，大型动物是家庭收入、储蓄和粮食供应的主要来源。这里获得的知识将使我们更好地了解如何控制这种疾病和相关疾病，如血吸虫病，并在以下方面对加拿大有好处：（一）了解寄生虫如何感染牛羊;（二）新的专利产品;（三）更好的诊断测试;（四）培训高素质的学生;（五）加强对疾病的预防和控制。㈤在协助发展中国家在粮食生产方面实现自我维持方面发挥领导作用。