@article{5c53949cf6b54d0d980b6bce44f508c4,
title = "Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulence",
abstract = "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.",
keywords = "Endothelial receptors, Intravital microscopy, Parasites, Tropism, Trypanosoma brucei, Vasculature",
author = "Niz, {Mariana de} and Daniela Br{\'a}s and Marie Ouarn{\'e} and Mafalda Pedro and Nascimento, {Ana M.} and {Henao Misikova}, Lenka and Franco, {Cl{\'a}udio A.} and Figueiredo, {Luisa M.}",
note = "Funding Information: The authors thank Brice Rotureau (Institut Pasteur) for providing the triple reporter (TY1-TdTomato-FLuc) AnTat1.1 E T. brucei parasite line. We thank Ruy M. Ribeiro for helpful advice for statistical analysis and Leonor Pinho for logistical help regarding experimental setups. We acknowledge the Rodent and Bioimaging Facilities of the Instituto de Medicina Molecular. We thank Maria Angeles Dominguez Cejudo from Claudio Franco{\textquoteright}s lab (IMM) for technical support. We also thank Francisca Vasconcelos, Sara Silva Pereira, Fabien Guegan, and Idalio Viegas for carefully reading this manuscript and providing helpful and critical feedback. This work was supported by HFSP ( LT000047/2019-L ) and EMBO ( ALTF 1048-2016 ) to M.D.N. L.M.F. is an Investigator CEEC of the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia ( CEECIND/03322/2108 ), and the laboratory is funded by ERC (FatTryp, ref. 771714 ). C.A.F. was supported by a European Research Council starting grant ( 679368 ), the Fondation Leducq ( 17CVD03 ), and the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (grants IF/00412/2012 , EXPL/BEX-BCM/2258/2013 , PRECISE-LISBOA-01-0145-FEDER-016394 , PTDC/MED-PAT/31639/2017 , PTDC/BIA-CEL/32180/2017 , and CEECIND/04251/2017 ). Funding Information: The authors thank Brice Rotureau (Institut Pasteur) for providing the triple reporter (TY1-TdTomato-FLuc) AnTat1.1E T. brucei parasite line. We thank Ruy M. Ribeiro for helpful advice for statistical analysis and Leonor Pinho for logistical help regarding experimental setups. We acknowledge the Rodent and Bioimaging Facilities of the Instituto de Medicina Molecular. We thank Maria Angeles Dominguez Cejudo from Claudio Franco's lab (IMM) for technical support. We also thank Francisca Vasconcelos, Sara Silva Pereira, Fabien Guegan, and Idalio Viegas for carefully reading this manuscript and providing helpful and critical feedback. This work was supported by HFSP (LT000047/2019-L) and EMBO (ALTF 1048-2016) to M.D.N. L.M.F. is an Investigator CEEC of the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (CEECIND/03322/2108), and the laboratory is funded by ERC (FatTryp, ref. 771714). C.A.F. was supported by a European Research Council starting grant (679368), the Fondation Leducq (17CVD03), and the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (grants IF/00412/2012, EXPL/BEX-BCM/2258/2013, PRECISE-LISBOA-01-0145-FEDER-016394, PTDC/MED-PAT/31639/2017, PTDC/BIA-CEL/32180/2017, and CEECIND/04251/2017). Conceptualization, M.D.N. C.A.F. and L.M.F.; methodology, M.D.N. M.O. L.H.M. and A.M.N.; software, M.D.N.; validation, D.B. and M.P.; formal analysis, M.D.N. C.A.F. and L.M.F.; investigation, M.D.N. D.B. M.O. and M.P.; data curation, M.D.N.; writing – original draft, M.D.N. C.A.F. and L.M.F.; writing – review & editing, M.D.N. C.A.F. and L.M.F.; visualization, M.D.N. with significant input from C.A.F. and L.M.F.; supervision, C.A.F. and L.M.F.; project administration, M.D.N. C.A.F. and LM.F.; funding acquisition, M.D.N. C.A.F. and L.M.F. The authors declare no competing interests. We worked to ensure diversity in experimental samples through the selection of the cell lines. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = sep,
day = "21",
doi = "10.1016/j.celrep.2021.109741",
language = "English",
volume = "36",
journal = "Cell reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",
}