Abstract
African trypanosomiasis is a tsetse fly transmitted disease indigenous for the African continent. Millions of people in 36 sub-Saharan African countries are currently at risk of this fatal infection. The current drugs are faced with limitations of toxicity and drug resistance and to date not a single effective vaccine is available. For both vaccine development and elimination endeavours, an adequate understanding of the immunology of infection onset, disease progression and distribution of parasites to tissue sanctuary niches is crucial. Our recent work has identified the skin and lungs as overlooked tissue reservoirs. Immunological studies in mouse models unveiled the increased presence of γδ T cells in infected tissues and a profound importance of these cells in regulating parasite control and host survival. The current research initiative will investigate the complex dynamics of γδ T cells during Trypanosoma brucei infections. The project consists of three distinct work packages (WP1-3). WP1 focuses on characterizing tissue-specific γδ T cell subsets following a natural, tsetse fly-transmitted T. brucei infection, focussing on their tissue tropism and contribution to immune cell recruitment and pathology. WP2 aims to explore the molecular mechanisms underlying the immune response of γδ T cells against T. brucei parasites, including their interaction with the major variant-specific surface glycoprotein (VSG) of the parasite. In vitro studies will inform about the responsiveness and functional importance of gene expression patterns of γδ T cells to parasitic stimulation. WP3 investigates the role of γδ T cells in the development of antiparasitic adaptive immunity and post-treatment tissue repair. This research employs advanced techniques such as single-cell transcriptomics, multiparameter immunoprofiling, and histopathological examinations in unique infection models to unravel the intricate interplay between γδ T cells and T. brucei, offering unprecedented basic scientific insights and revealing opportunities for immunotherapeutic interventions against trypanosomiasis.
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