Cholinergic control of innate and adaptive immunity to gastrointestinal parasites

线虫寄生虫（蛔虫）在农场动物中引起严重疾病，特别是绵羊和牛，并在英国和世界范围内造成重大经济损失。通过药物治疗可以控制感染，但蛔虫很快就会对所有可用的药物产生耐药性，这种现象称为多药耐药性。虽然正在开发新药，但蛔虫可能会对这些药物产生抗药性，因此迫切需要开发其他疾病控制手段，以保护和加强畜牧业生产。接种疫苗是显而易见的替代方案，但迄今为止证明很难。对蛔虫的免疫是由所谓的“2型”反应介导的，如果我们有更好的方法来驱动这些反应，抗蛔虫疫苗很可能会得到改进。我们已经发现，一种称为ACh的信号分子对于线虫感染的最佳宿主免疫是必不可少的，并且表明在启动2型反应中重要的细胞产生这种分子。寄生虫产生一种酶，以乙酰胆碱，我们认为，这是重要的抑制宿主免疫反应，促进他们的生存。在这个项目中，我们的目标是确定这种信号分子促进对蛔虫免疫的机制，以及蛔虫如何保护自己免受其害。这对于设计新的策略来提高疫苗预防蛔虫感染的能力非常重要。

Nematode parasites (roundworms) cause severe disease in farm animals, in particular sheep and cattle, and are responsible for significant economic losses both in the UK and worldwide. Infection is controlled by treating the animals with drugs, but the roundworms are quickly becoming resistant to all available products, a phenomenon known as multidrug resistance. Although new drugs are being developed, the likelihood is that the roundworms will develop resistance to these in turn, so there is an urgent need to develop other means of disease control in order to protect and intensify livestock production. Vaccination is the obvious alternative, but has proven difficult thus far. Immunity to roundworms is mediated by what are known as 'type 2' responses, and it is likely that anti-roundworm vaccines could be improved if we had better means to drive these. We have discovered that a signalling molecule called ACh is essential for optimal host immunity to nematode infection, and shown that a cell which is important in kick-starting type 2 responses makes this molecule. Parasites produce an enzyme to inactivate ACh, and we suggest that this is important for inhibiting host immune responses and promoting their survival. In this project, we aim to define the mechanisms whereby this signalling molecule promotes immunity to roundworms, and how the roundworms defend themselves against it. This is important for designing new strategies to improve the ability of vaccines to protect against roundworm infection.