Bioengineered 3D microvessels and complementary animal models reveal mechanisms of Trypanosoma congolense sequestration

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 26, 2025

Abstract In the mammalian host, Trypanosoma congolense cytoadheres, or sequesters, to vascular endothelium. Although sequestration influences clinical outcome, disease severity and organ pathology, its determinants mediators remain unknown. Challenges such as variability of animal models, only-recently developed tools genetically manipulate parasite, lack physiologically-relevant in vitro models have hindered progress. Here, we engineered brain cardiac 3D bovine endothelial microvessel that mimic microvasculature aorta, respectively. By perfusing these with two T. strains, investigated roles flow for parasite tropism different beds. We discovered is dependent on cyclic adenosine monophosphate (cAMP) signalling, closely linked proliferation, but not associated transmission tsetse fly vector. Finally, by comparing expression profiles sequestered non-sequestered parasites collected from a rodent model, showed gene changes parasites, including surface variant antigens. This work presents platform study trypanosome interactions vasculature provides deeper understanding molecular biophysical mechanisms underlying sequestration.

Language: Английский

Bioengineered 3D microvessels reveal novel determinants of Trypanosoma congolense sequestration

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 25, 2024

In the mammalian host, Trypanosoma congolense cytoadheres to vascular endothelium in a process known as sequestration. Although sequestration influences clinical outcome, disease severity and organ pathology, its determinants mediators remain unknown. Challenges such variability of animal models, only-recently developed tools genetically manipulate parasite, lack physiologically relevant in vitro models have hindered progress. Here, we engineered brain cardiac 3D bovine endothelial microvessel that mimic microvasculature aorta, respectively. By perfusing these with two T. strains, simulated conditions investigated roles flow for parasite tropism different beds. We discovered is dependent on cyclic AMP signalling, closely linked proliferation, but not associated transmission tsetse fly vector. Finally, by comparing expression profiles sequestered non-sequestered parasites collected from rodent model, showed gene changes parasites, including surface variant antigens. This work presents physiologically-relevant platform study trypanosome interactions vasculature provides deeper understanding molecular biophysical mechanisms underlying

Language: Английский