Abstract
Understanding African Trypanosomiasis (AT) host-pathogen interaction is the key to an “anti-disease vaccine”, a novel strategy to control AT. Here we provide a better insight into this poorly described interaction by characterizing the activation of a panel of endothelial cells by bloodstream forms of four African trypanosome species, known to interact with host endothelium. T. congolense, T. vivax, and T. b. gambiense activated the endothelial NF-κB pathway, but interestingly, not T. b. brucei. The parasitic TS (trans-sialidases) mediated this NF-κB activation, remarkably via their lectin-like domain and induced production of pro-inflammatory molecules not only in vitro but also in vivo, suggesting a considerable impact on pathogenesis. For the first time, TS activity was identified in T. b. gambiense BSF which distinguishes it from the subspecies T. b. brucei. The corresponding TS were characterized and shown to activate endothelial cells, suggesting that TS represent a common mediator of endothelium activation among trypanosome species with divergent physiopathologies.
Highlights
Animal African trypanosomiasis (AAT) is a severe disease affecting livestock in sub-Saharan Africa throughout an area of approximately 10 million km2, and causing annual economic losses of several billion dollars [1,2]
We clearly demonstrated that animal African trypanosomes activate the endothelial cells via the NF-kB pathway and cause a pro-inflammatory response in vitro and in vivo via their TS
By comparing four different trypanosomes species, we showed that they displayed distinct capacities for activation
Summary
Animal African trypanosomiasis (AAT) is a severe disease affecting livestock in sub-Saharan Africa throughout an area of approximately 10 million km, and causing annual economic losses of several billion dollars [1,2]. The disease is characterized by severe anaemia, weight loss and immunosupression, leading to the death of the animal if not treated. It is caused by the parasites Trypanosoma congolense, Trypanosoma vivax and to a lesser extent, Trypanosoma brucei. Human African trypanosomiasis (HAT), known as sleeping sickness, affects mostly poor populations living in rural areas of Africa with ,10 000 new cases reported per year according to World Health Organization reports. Almost 90% of the reported HAT cases are caused by Trypanosoma brucei gambiense
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