Proteomic approach to characterisation of pathogenesis mechanisms in fasciolosis

肝吸虫病是由肝片吸虫和大片吸虫(热带肝吸虫)感染绵羊和牛引起的。这种感染每年给非洲、亚洲、S和北美以及欧洲的农业部门造成超过30亿美元的经济损失，感染动物超过5亿只。寄生虫通过摄入受污染的植物或水中的感染性包囊传播。如果寄生虫侵入肝脏，导致出血性病变和贫血。我们的目标是通过识别被认为在感染中重要的宿主和寄生虫因素来帮助开发有效的控制片状吸虫的疫苗或药物。我们正在应用一种新的方法，使用一种名为“生物标记物分析”的技术，来识别受感染动物血清中作为疾病生物标记物的因素。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素的指示器。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来建立感染；我们的目标也是开发更好的疾病诊断测试。肝吸虫病的一个特征是肝片吸虫和巨型肝片吸虫在动物体内的毒力不同；绵羊对巨型肝片吸虫获得抗药性，但不能获得抗药性。这表明这两种寄生虫在一些关键特征上存在差异(S)，这使得巨型肝片吸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记物图谱来理解这种行为上的差异：表达不同的生物标记物代表毒力因子，而毒力因子是药物/疫苗治疗的主要目标。这项工作对世界各地的初级生产者，包括非洲和亚洲的自给自足的农民来说很重要，在这些地区，大型动物是家庭收入、储蓄和食物供应的主要来源。在这里获得的知识将使我们更好地了解如何控制这一疾病和血吸虫病等相关疾病，并在以下方面对加拿大有利：(1)了解寄生虫如何感染牛和羊；(2)新的可申请专利的产品；(3)更好的诊断测试；(4)培训高素质学生；(5)在帮助发展中国家在粮食生产方面实现自给自足方面发挥领导作用。

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.