Pilot study to develop a novel model to investigate the mechanisms and consequences of foetal immune programming on immune fitness through life

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How the immune system develops in early life is critical for defining immune fitness throughout adult life. The immune challenges which we are exposed to in early life play an important role in training the immune system, teaching it what to respond to, and how strongly to respond. Getting this balance right is critical for health in adult life, with dysregulated immunity leading to disease, such as allergies, autoimmunity, mental illnesses, and obesity.Foetal development during gestation is a critical period of immune development, and the immune challenges faced by the mother influence how the baby's immune system develops. Infections in the mother alter foetal immune development, and can change the way the offspring responds in adult life to infections and allergies. Our group studies immunity to parasitic worms, which are a huge worldwide human health burden, and large economic burden for the livestock industry. They are very good at evading or suppressing immune responses, allowing them to survive for decades in their host. Maternal helminth infections are known to influence foetal immune development, and can suppress offspring immunity resulting in a lower level of immune responsiveness in later life. This can make them more susceptible to future infections, and can also impair their ability to respond to vaccination. However, it can also have beneficial effects, and can make them less susceptible to allergies. However, the mechanisms by which this occurs are unknown.Unfortunately, it is very difficult to perform mechanistic work in humans, and there is a lack of experimental animal models. The goal of this proposal is to develop a new mouse model that will allow us investigate how helminth infection during pregnancy influences the development of the baby's immune system, and how this impacts their immune balance and health during adulthood. This will help identify why some immune challenges during pregnancy turn off the baby's immune responses, increasing infection susceptibility and lowering vaccine responsiveness and the risk of developing diseases, whilst other immune challenges activate the baby's immune system increasing their risk of diseases in later life. This will increase our fundamental knowledge, and this knowledge can be used to identify early-life disease associated risk markers allowing us to predict health in later life. It can also be used to suggest strategies to manipulate immune development during early life to prevent individuals subsequently developing disease. Identifying how maternal helminth infections inhibit the ability of offspring to respond to vaccinations is important for the development of vaccine strategies for helminth and non-helminth infections in both livestock and humans.