The impact of gastrointestinal helminths on susceptibility to African trypanosome infections

African trypanosomes are extracellular protozoan parasites that are transmitted between mammals by tsetse flies. These parasites cause chronic infections in the mammalian bloodstream (African trypanosomiasis), inflicting economic strain on African livestock industries. Much of our understanding of African trypanosomiasis is derived from experimental transmissions of individual parasite strains to mice or cattle. However, in natural settings co-infections with other pathogens within the same host species are common. For example, pathogens including malarial parasites, gastrointestinal helminth parasites, Mycobacterium tuberculosis and viruses such as HIV may affect up to a third of the human population in some developing countries. Increasing evidence shows that co-infection with these pathogens can alter susceptibility to other important pathogens, and influence vaccine efficacy by affecting host immune function. In the UK as the population begins to emerge from the COVID-19 restrictions, the impacts of influenza virus co-infection on susceptibility to the SARS-CoV-2 coronavirus are uncertain. Co-infection with some pathogens may also hinder the accuracy of diagnostic tests against other pathogens.
Studies in mice show that the immune response to a gastrointestinal helminth infection can alter susceptibility to co-infection to many other bacterial and viral pathogens including Salmonella enterica serovar Typhimurium, Citrobacter rodentium and norovirus. Although livestock species such cattle and buffalo are regularly exposed to gastrointestinal helminth parasites, nothing is known of how co-infection with these parasites may affect susceptibility to African trypanosomes. Therefore, the first major aim of this project is to test the hypothesis that co-infection with gastrointestinal helminths significantly influences susceptibility to African trypanosome infections.
During African trypanosome infections the body's macrophages are activated to clear the parasites. However, the over-reaction of these pro-inflammatory macrophages to the trypanosome infection can cause immunopathology and suppress antigen-specific immunity. Conversely, during helminth infections the macrophages adopt an alternatively-activated phenotype that plays an important role in immune regulation and repairing tissue damage. Whether African trypanosome infections can modulate macrophage polarity and function in response to helminths is unknown. Therefore, the second major aim of this project is to test the hypothesis that the potent pro-inflammatory macrophage response that is induced in African trypanosome infections negatively impacts on the ability of macrophages to repair the damage caused by helminths in the intestine.
No vaccines are available against African trypanosome infections, and the development of resistance to commonly used trypanocidal drugs is a constant issue. A thorough understanding how factors such as pathogen co-infection can affect susceptibility to African trypanosomiasis will help reveal novel targets for effective intervention and prevention.
This project will utilize mouse gastrointestinal helminth and African trypanosome infection models that are available in the supervisors' laboratories. The project brings together several important biological disciplines, including parasitology, mucosal immunology and bio-imaging. This will provide the student with excellent training opportunities in the following important transferable skills: in vivo biology; state-of-the-art bio-imaging; cell culture; transcriptomics.