Analysis of the secretome of parasitic nematodes

人类和动物感染丝虫病在热带医学和兽医学中具有重要的临床意义。例子包括淋巴丝虫病，由寄生虫如马来丝虫引起。成年寄生虫生活在人类的淋巴系统中，其后代称为微丝蚴，存在于血液中。 这种寄生虫会导致一种名为象皮病的显著的、使人衰弱的疾病，在这种疾病中，受影响的身体部位，如腿，会肿胀到大象的比例。犬心丝虫感染由犬心丝虫引起，是北美大部分地区兽药使用的主要适应症;该种属的成虫生活在心肺循环的大血管中，可导致犬的严重健康问题。 微丝蚴在血液中循环。与大多数线虫感染一样，这些寄生虫对其宿主具有相当特异性。 事实上，宿主动物对绝大多数寄生虫物种的感染不敏感;只有少数寄生虫物种能够在任何特定宿主中成功感染。 这种宿主-寄生虫特异性是如何建立的，几乎对所有寄生虫都是未知的。 了解为什么一些寄生虫能够克服宿主的高效抗寄生虫防御，将确定控制这些感染的全新方法。 然而，在实现这一目标之前，我们必须在分子水平上深入了解寄生虫如何逃避宿主防御。我们的目标是表征微丝蚴分泌的整套蛋白质（称为“分泌组”），这些蛋白质保护微丝蚴免受宿主免疫反应的破坏，宿主免疫反应通常在清除血液中的异物方面非常有效。 此外，我们将研究这些寄生虫的分泌过程的生物学，以了解寄生虫如何部署它以建立成功的感染。

Infections of humans and animals with parasitic nematodes called filariae are of great clinical significance in tropical and veterinary medicine. Examples include lymphatic filariasis, caused by parasites such as Brugia malayi. Adult parasites live in the lymphatic system of humans, with their progeny, termed microfilariae, being found in the blood.  This parasite can lead to the remarkable and debilitating condition called elephantiasis, in which affected body parts, such as the legs, can swell to elephantine proportions. Canine heartworm infections, caused by Dirofilaria immitis, are a major indication for veterinary drug use in most of North America; adult worms of this species live in the large blood vessels in the cardiopulmonary circulation and can cause significant health problems in dogs.  The microfilariae are found circulating in the blood. As is true for most nematode infections, these parasites are quite specific for their hosts.  Indeed, host animals are not susceptible to infection by the vast majority of parasite species; only a few parasite species are capable of mounting a successful infection in any particular host.  How this host-parasite specificity is established is unknown for almost all parasites.  Understanding why a few parasites are able to overcome the otherwise highly effective antiparasitic defenses of hosts will identify completely new approaches to the control of these infections.  Before that goal can be realized, however, we must develop a thorough understanding of how parasites evade host defenses at a molecular level. Our aim is to characterize the entire set of proteins secreted by microfilariae (called the 'secretome') that protect them from destruction by the host immune response, which is normally so efficient at removing foreign objects from the blood.  In addition, we will study the biology of the secretory process of these parasites in order to comprehend how the parasite deploys it to establish a successful infection.