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Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulence
Publication . De Niz, Mariana; Brás, Daniela; Ouarné, Marie; Pedro, Mafalda; Nascimento, Ana M.; Henao Mišíková, Lenka; Franco, Claudio; Figueiredo, Luisa M.
Trypanosoma brucei is responsible for lethal diseases in humans and cattle in Sub-Saharan Africa. These extracellular parasites extravasate from the blood circulation into several tissues. The importance of the vasculature in tissue tropism is poorly understood. Using intravital imaging and bioluminescence, we observe that gonadal white adipose tissue and pancreas are the two main parasite reservoirs. We show that reservoir establishment happens before vascular permeability is compromised, suggesting that extravasation is an active mechanism. Blocking endothelial surface adhesion molecules (E-selectin, P-selectins, or ICAM2) significantly reduces extravascular parasite density in all organs and delays host lethality. Remarkably, blocking CD36 has a specific effect on adipose tissue tropism that is sufficient to delay lethality, suggesting that establishment of the adipose tissue reservoir is necessary for parasite virulence. This work demonstrates the importance of the vasculature in a T. brucei infection and identifies organ-specific adhesion molecules as key players for tissue tropism.
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Fundação para a Ciência e a Tecnologia
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3599-PPCDT
Número da atribuição
153415