Glucagon-like peptide-1; a gut hormone with the capacity to be pivotal in mammalian helminth infection

Intestinal helminth infection causes morbidity in millions of the world’s most deprived communities and often causes nutritional impairment. Helminth infection alters hormone-secreting enteroendocrine cells (EECs) of the intestinal epithelium, which respond to luminal nutrients by secreting peptide hormones to coordinate efficient digestion and nutrient absorption. As the intestinal epithelium must also act as a barrier against potential pathogens, it communicates with immune cells present in the intestine, which comprise the largest collection of immune cells in any tissue of the body. However, how EECs of the intestinal epithelium regulate the immune system during helminth infection is poorly understood.

This project will examine the novel hypothesis that EECs secrete the hormone glucagon-like peptide 1 (GLP-1) in response to sensing helminths. GLP-1 can then act as a cytokine to directly control the function of lymphocyte populations in the epithelium. I will then determine whether GLP-1 receptor agonist drugs, already in clinical use for diabetes, can be repurposed for use for during helminth infection.

My project will uncover key mechanisms by which the immunoendocrine axis regulates immunity in the intestine which can inform new therapies for inflammatory diseases and infections of the intestine.