PROTEASES OF SCHISTOSOMES IN HOST-PARASITE INTERACTION

Schistosomiasis (bilharziasis), caused by parasitic flatworms called schistosomes, is a major global health problem with more than 240 million people infected worldwide. Schistosomes are masters in modulating the host immune responses that allow them to survive in the host for many years. They induce very diverse immune responses in contrast to bacteria, fungi, viruses, or protozoa. Schistosoma infection and Schistosoma-derived molecules lead to induction of certain immune responses, which characterises the response to helminth infection, as well as allergic reactions. Proteolytic enzymes (proteases) are crucial for successful parasitism of schistosomes, including the invasion, nutrient intake, maturation, reproduction, and immune evasion. In contrast to proteolytic allergens, such as the major house dust mite allergen Der p 1 or papain, the recognition of helminth proteases by host and signalling pathways activated remain poorly characterized, and thus are the focus of this project. We will focus three different cysteine proteases of Schistosoma mansoni: cathepsin B1, cathepsin L3, and cathepsin B2. They will be produced as recombinant proteins by heterologous expression in yeast Pichia pastoris. Their interaction with the mammalian host cells will be analysed in vitro and in vivo. These experiments will lead to the identification of the host cell populations, receptors, and molecular mediators involved in the host-protease interactions. The interdisciplinary project integrates several aspects: enzyme biochemistry, immunology, molecular parasitology and focuses on the interaction of the mucosal immune system with schistosomal cysteine proteases that have not been studied so far. The project will provide new information on trematode proteases not only as potential targets for new anti-parasite therapeutic strategies but also as interesting modulators of host physiological and immunological processes.