Unravelling host intestine-parasite interactions that define immune responses to whipworms

ended

Whipworms (Trichuris trichuira) are soil-transmitted helminths that infect about 700 million people in the tropics and sub-tropics and cause the human disease, trichuriasis. Whipworms live preferentially in the cecum of their hosts where they tunnel through epithelial cells and cause inflammation potentially resulting in colitis. Despite extensive research, the role of whipworm interactions with epithelial and immune cells in triggering parasite expulsion remains unclear, hindering the development of anti-parasite therapies. The ultimate goal of my research proposal is to investigate and understand this interaction in detail. To achieve this, I will use T. muris, a mouse model of T. trichuira infection in humans. This research proposal has three key aims. First, to identify new parasite and host genes that could interplay and modulate immunological outcomes. Second, to characterize the role of host genes in whipworm infection and immunity. Here, novel and known candidate mutations conferring susceptibility to colitis identified through the Wellcome Trust Sanger Institute - Mouse Genetics Project will be targeted. Thus, I will challenge mutant mouse lines with T. muris and evaluate the influence of these mutations on anti-parasite immunity and expulsion. Finally, upon identification of key genes regulating the immune response to whipworms, I will explore the mechanism of action of selected genes and their effect on the parasite. For this, I will take advantage of the vast range of ‘omic’ technologies and facilities available at the WTSI. This project will generate novel fundamental data on host-whipworms interactions and also support future efforts to control these parasites by the identification of potential new therapeutic targets. Moreover, resulting knowledge of the parasiteimmunological interplay could be exploited to understand other intestinal inflammatory diseases such as ulcerative colitis that have many similarities with trichuriasis.