Cholinergic control of innate and adaptive immunity to gastrointestinal parasites

点击翻译按钮获取中文摘要

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.