Proteomic approach to characterisation of pathogenesis mechanisms in fasciolosis

肝吸虫病是由寄生虫肝片吸虫病和热带肝吸虫病感染绵羊和牛引起的。这种感染每年给非洲、亚洲、南美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，有超过5亿只动物受到感染。这种寄生虫是通过食用受污染的植物或水而摄入感染囊而传播的。寄生虫侵入肝脏，引起出血性病变和贫血。我们的目标是通过识别在感染中被认为重要的宿主和寄生虫因素，协助开发有效的疫苗或药物来控制片形吸虫。我们正在采用一种新方法，使用一种称为“生物标志物分析”的技术，来确定受感染动物血清中作为疾病生物标志物的因素。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；我们还致力于开发更好的疾病诊断测试。肝吸虫病的一个特点是肝吸虫和巨吸虫在动物中的毒力不同；绵羊获得了对巨型F.虫的抗性，但没有对肝F.虫的抗性，这表明这两种寄生虫在某些关键特性上有所不同，这使得巨型F.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两种寄生虫的生物标志物谱来理解这种行为差异：表达不同的生物标志物代表毒力因子，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很重要，包括非洲和亚洲的自给农民，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。在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血吸虫病等相关疾病，并在以下方面对加拿大有益：(i)了解寄生虫如何感染牛羊；（二）新的可授予专利的产品；㈢更好的诊断测试；（四）培养高素质人才；（五）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。

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.