Analysis of the secretome of parasitic nematodes

人和动物感染被称为丝虫的寄生线虫在热带医学和兽医学中具有重要的临床意义。例如由马来丝虫等寄生虫引起的淋巴丝虫病。成年寄生虫生活在人类的淋巴系统中，他们的后代被称为微丝虫，在血液中被发现。这种寄生虫可能会导致一种名为象皮病的显著和虚弱的情况，在这种情况下，受影响的身体部位，如腿，可以膨胀到大象的比例。犬心虫感染是由吸浆线虫引起的，在北美大部分地区是使用兽药的主要适应症；该物种的成虫生活在心肺循环中的大血管中，可能会给狗造成重大健康问题。但在血液中发现了微丝虫。就像大多数线虫感染一样，这些寄生虫对它们的宿主是非常特异的。事实上，宿主动物不容易被绝大多数寄生虫物种感染；只有少数寄生虫物种能够在任何特定宿主上成功地感染。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是未知的。了解为什么少数寄生虫能够克服宿主的高效抗寄生虫防御将找到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彻底了解寄生虫是如何逃避宿主防御的。我们的目标是确定微丝虫所分泌的一整套蛋白质的特征，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将异物从血液中清除。此外，我们还将研究这些寄生虫的分泌过程的生物学，以了解寄生虫如何利用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.