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Projeto de investigação
Exploring the hidden life of African trypanosomes: parasite fat tropism and implications for disease
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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 Misikova, Lenka; Franco, Claudio A.; Figueiredo, Luisa M.; DCV - Departamento de Ciências da Vida; Elsevier
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.
Adipocyte metabolic response to Trypanosoma brucei in a co-culture setting
Publication . Pereira, Ana Raquel Santos; Figueiredo, Luísa
African trypanosomiasis is a vector-borne disease caused by extracellular protozoan parasites, including Trypanosoma brucei. The establishment of infection in mammalian hosts is characterized by invasion of the bloodstream and solid tissues. Among these, the adipose tissue (AT) is heavily colonized by T. brucei in mice. During infection there is also a large reduction of AT mass which suggests the mobilization of lipids stored in the adipocyte. However, it is not known how adipocyte to parasite interactions may contribute to adipocyte lipid metabolism. Here we show that co-culturing 3T3-L1 adipocytes and T. brucei in vitro increased adipocyte lipolysis. We
found that this increase can be elicited by a soluble parasite factor, but it is larger when live parasites are in direct contact with adipocytes. Furthermore, chemical inhibition of adipose triglyceride lipase (ATGL) during co-culture lead to a reduction of fatty acid and glycerol release, indicating that the release of lipolytic products in the presence of T. brucei is an ATGL-dependent mechanism. Overall, the findings in this study indicate that T. brucei is able to directly modulate adipocyte catabolism, highlighting the need to further investigate the molecular partners involved in this host-parasite interaction.
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Entidade financiadora
European Commission
Programa de financiamento
H2020
Número da atribuição
771714