Analysis of the secretome of parasitic nematodes

被称为丝虫的寄生虫感染的人与动物在热带医学和兽医学中具有重要的临床意义。这方面的例子包括淋巴丝虫病，它是由马来布鲁吉亚虫等寄生虫引起的。成年寄生虫生活在人类的淋巴系统中，它们的后代被称为微丝虫病，存在于血液中。这种寄生虫会导致令人虚弱的象皮病，在这种情况下，受影响的身体部位，如腿，会膨胀到象皮病的比例。犬心丝虫感染是由免疫Dirofilaria引起的，是北美大部分地区兽药使用的主要指征；这种成虫生活在心肺循环的大血管中，会对狗造成严重的健康问题。微丝蚴在血液中循环。就像大多数线虫感染一样，这些寄生虫对它们的宿主有很强的特异性。事实上，宿主动物不容易受到绝大多数寄生虫物种的感染；只有少数几种寄生虫能够成功地感染任何特定的宿主。对于几乎所有寄生虫来说，这种宿主-寄生虫特异性是如何建立的尚不清楚。了解为什么少数寄生虫能够克服宿主高度有效的抗寄生虫防御，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，我们必须彻底了解寄生虫如何在分子水平上逃避宿主的防御。我们的目标是描述微丝虫分泌的一整套蛋白质（称为“分泌组”）的特征，这些蛋白质保护它们免受宿主免疫反应的破坏，宿主免疫反应通常能有效地清除血液中的异物。此外，我们将研究这些寄生虫分泌过程的生物学，以了解寄生虫如何部署它来建立成功的感染。

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.