Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulence.
Adipose Tissue, White
/ parasitology
Animals
Antibodies
/ immunology
Antigens, CD
/ immunology
CD36 Antigens
/ metabolism
Cell Adhesion Molecules
/ immunology
E-Selectin
/ immunology
Human Umbilical Vein Endothelial Cells
Humans
Male
Mice
Mice, Inbred C57BL
P-Selectin
/ immunology
Pancreas
/ parasitology
Parasitemia
/ mortality
Survival Rate
Trypanosoma brucei brucei
/ pathogenicity
Up-Regulation
Virulence
Trypanosoma brucei
endothelial receptors
intravital microscopy
parasites
tropism
vasculature
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
21 09 2021
21 09 2021
Historique:
received:
02
04
2021
revised:
29
06
2021
accepted:
28
08
2021
entrez:
22
9
2021
pubmed:
23
9
2021
medline:
16
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34551286
pii: S2211-1247(21)01194-3
doi: 10.1016/j.celrep.2021.109741
pmc: PMC8480282
pii:
doi:
Substances chimiques
Antibodies
0
Antigens, CD
0
CD36 Antigens
0
Cell Adhesion Molecules
0
E-Selectin
0
ICAM-2 protein, mouse
0
P-Selectin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109741Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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