Scrutinizing the role of mast cell during human and murine Trypanosoma infections.

Human African trypanosomiasis is a tsetse fly-transmitted disease indigenous for the African continent. Millions of people in 36 countries in sub-Saharan Africa are currently at risk of this often fatal infection. The drugs that are currently available are faced with limitations of toxicity and drug resistance and not a single effective vaccine is yet available. For both vaccine development and elimination endeavours, an adequate understanding of the immunology of infection onset is crucial. Mast cells (MCs) are immune sentinels in the skin that are amongst the first to contact the Trypanosoma parasite following a tsetse fly bite. These cells play major roles in orchestrating early inflammatory responses, regulating vascular permeability and influencing immunity development in lymph nodes. Despite seminal work in mosquito-transmitted viral diseases, MCs remain underexplored as target cell during parasitic infections. Combining our expertise in MCs and our work with Trypanosoma as well as the possibility to use the natural vector in our inhouse insectary, the role of MCs will be assessed in natural Trypanosoma infections. Using human MCs derived from progenitors in donor blood, a battery of cellular activation markers will provide insights in the interaction with the Trypanosoma parasite and tsetse fly-derived components. The mast cell role will be further explored in appropriate animal models of mast cell deficiency following a natural infection by a tsetse fly bite. To summarize, the preliminary results of our in vitro and in vivo experiments will provide insight towards novel intervention strategies and foundations for future research.

Keywords:MAST CELLS, IMMUNE RESPONSE, TRYPANOSOMA

Disciplines:Innate immunity, Infectious diseases, Parasitology