Critical early events at the mucosal/worm interface following infection fo sheep with the abomasal nematode Teladorsagia circumcincta

摘要：由毛圆线虫引起的寄生虫性胃肠炎（PGE）是英国绵羊最常见的全身性疾病，主要的致病线虫（蠕虫）是皱胃寄生虫环切端蝇（Teladorsagia circumcision）。从生产的角度来看，该综合征导致粮食利用率下降，生长率下降，胴体和羊毛质量下降，简而言之，生产者的经济损失损害了经济可行性。由于目标线虫迅速出现耐药性，依赖于使用驱虫药的控制正在失败。疫苗接种是一种可行的替代方案，但由于缺乏对宿主-寄生虫与进入的幼虫相互作用的了解，发展受到阻碍，而幼虫是绵羊免疫的主要影响因素。随着这种反应的发展，它被认为会导致幼虫发育受阻，这是导致断奶羔羊患病的一个主要因素。在这里，我们将试图定义感染宿主部位（真正的胃或皱胃）和进入的幼虫之间的分子相互作用，目的是确定宿主驱逐蠕虫和蠕虫蛋白所需的机制，刺激它们或被它们靶向。我们将定义宿主基因表达在皱胃表面层，以响应传入的幼虫，并独特地将此分析与幼虫的等效分析相比较。目的是将宿主对寄生虫的关键早期反应与寄生虫基因表达的发育变化联系起来，其中一些基因表达可能是由宿主诱导的，并在宿主体内形成抗寄生虫免疫时影响寄生虫的生存策略。这项工作将使我们能够确定潜在的候选疫苗，并提供优化疫苗递送所需的基本信息，从而使通过接种控制更进一步。

SUMMARY Parasitic gastroenteritis (PGE), caused by trichostrongylid nematodes, is the most commonly diagnosed systemic disease of sheep in the U.K. The principal causative nematode (worm) is the abomasal parasite Teladorsagia circumcincta. From a production perspective, the syndrome causes impaired food utilisation, poor growth rates as well as poor carcass and fleece quality, in short, economic loses for the producer which compromise economic viability. Control, dependent on the use of anthelmintics, is failing due to the rapid emergence of drug resistance in the target nematodes. Vaccination is a feasible alternative but development is hampered by a lack of knowledge of the host-parasite interaction to incoming larvae, a prime effector of immunity in sheep. As this response develops, it is thought to induce arrested larval development, a factor which makes a major contribution to disease in the weaned young lamb. Here we will seek to define the molecular interactions between the host site of infection (the true stomach or abomasum) and the incoming larvae, the purpose being to identify the host mechanisms required to expel the worms and the worm proteins stimulating these or being targeted by them. We will define host gene expression in the abomasal surface layer in response to incoming larvae and, uniquely, parallel this analysis with the equivalent in the larvae. The purpose is to correlate key early host responses to the parasite with developmental changes in parasite gene expression, some of which are likely to be induced by the host and effect a parasite survival strategy in the face of developing anti-parasite immunity in the host. This work will allow us to identify potential vaccine candidates and provide basic information required to optimise vaccine delivery bringing control by vaccination a step closer.