Host-parasite interaction as a model to define immunological regulatory pathways.

人们常常有一种误解，认为寄生虫病仅限于世界热带地区。这远非事实。在加拿大可以感受到寄生虫病的影响，那里的牲畜、伴侣动物和人类每年都可能遭受寄生虫感染，造成数百万美元的损失。在这个项目中，我们使用了一个方便的实验室模型系统——感染了大鼠绦虫（Hymenolepis miniuta）的小鼠模型——来提出一系列基本问题，这些问题涉及针对蠕虫（即蠕虫）寄生虫的免疫反应的基本问题，以及如何利用这些知识来对抗蠕虫寄生虫感染、调节粘膜免疫和影响合并症。三个方面的调查被编织成一个统一的研究计划，该计划评估了蠕虫寄生虫影响宿主免疫的两种主要方式。首先，一系列的免疫学研究将确定伴随小虫感染的小鼠免疫细胞群的早期（即1-5天）变化，然后确定其中哪些驱动了负责驱逐蠕虫的适应性免疫反应。其次，关注一个免疫信号，即白细胞介素(IL)-10，我们将确定该分子在以下方面的作用：1)对寄生虫的排斥反应；2)动员一系列抗虫事件后免疫系统的恢复；3)发挥旁观者效应和抑制肠道或关节疾病相关炎症的能力。第三，分子分析将寻求从蠕虫中分离和表征生物活性分子，这些分子可能作为开发新型免疫抑制药物的蓝图。作为一个综合项目，本研究将为宿主-寄生虫（即蠕虫）相互作用的免疫学方面提供基础数据，可用于开发更好的抗虫治疗方法和开发操纵哺乳动物免疫反应的策略。

There is often the misconception that parasitic diseases are restricted to tropical regions of the world. This is far from the truth. The effects of parasitism are felt in Canada, where livestock, companion animals and humans can suffer from parasitic infections at the cost of millions of dollars annually. In this project we make use of a convenient laboratory model system - that of mice infected with the rat tapeworm, Hymenolepis diminuta - to ask a series of basic questions that address fundamental issues relating to the immune response directed at helminth (i.e. worm) parasites and how this knowledge can be used to both combat infection with helminth parasites, modualte mucosal immunity and affect co-morbidities. Three strands of investigation are woven into a unified research plan that assesses the two principal means by which helminth parasites can affect host immunity. First, a series of immunological studies will define the early (i.e. 1-5 days) changes in immune cell populations in mice that accompany infection with H. diminuta and then determine which of these drive the adaptive immune response responsible for expulsion of the worm. Second, focusing, on one immune signal, namely interleukin (IL)-10, we will determine the role for this molecule in (i) rejection of the parasite, (ii) recovery of the immune system after the mobilization of a spectrum of anti-worm events, and (iii) the ability to exert a bystander effect and suppress disease-related inflammation in the gut or joints. Third, a molecular analysis will seek to isolate and characterize bio-active molecules from the worm that may serve as blueprints for the development of novel immuno-suppressive drugs. As an integrated program, this study will provide fundamental data on immunological aspects of host-parasite (i.e. helminth) interactions that can be applied to the development of better anti-worm treatments and the development of strategies to manipulate the mammalian immune response.