Author(s):
De Niz, Mariana ; Brás, Daniela ; Ouarné, Marie ; Pedro, Mafalda ; Nascimento, Ana M. ; Henao Misikova, Lenka ; Franco, Claudio A. ; Figueiredo, Luisa M.
Date: 2021
Persistent ID: http://hdl.handle.net/10362/142772
Origin: Repositório Institucional da UNL
Project/scholarship:
info:eu-repo/grantAgreement/EC/H2020/771714/EU;
info:eu-repo/grantAgreement/EC/H2020/679368/EU;
info:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00412%2F2012%2FCP0163%2FCT0007/PT;
info:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FBEX-BCM%2F2258%2F2013/PT;
info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-PAT%2F31639%2F2017/PT;
info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-PAT%2F31639%2F2017/PT;
info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-CEL%2F32180%2F2017/PT;
Subject(s): endothelial receptors; intravital microscopy; parasites; tropism; Trypanosoma brucei; vasculature; Biochemistry, Genetics and Molecular Biology(all); SDG 7 - Affordable and Clean Energy
Description
LT000047/2019-L ALTF 1048-2016 CEECIND/03322/2108 17CVD03 PRECISE-LISBOA-01-0145-FEDER-016394 CEECIND/04251/2017
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.
