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

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-
    • Subject Terms:
      Trypanosoma congolense*/physiology ; Microvessels*/parasitology ; Trypanosomiasis, African*/parasitology; Brain/blood supply ; Brain/parasitology ; Endothelium, Vascular/parasitology ; Endothelial Cells/parasitology ; Animals ; Cattle ; Disease Models, Animal ; Host-Parasite Interactions
    • Abstract:
      In the mammalian host, Trypanosoma congolense cytoadheres, or sequesters, to the vascular endothelium. Although sequestration influences clinical outcome, disease severity and organ pathology, its determinants and mediators remain unknown. Challenges such as the variability of animal models, the only-recently developed tools to genetically manipulate the parasite, and the lack of physiologically-relevant in vitro models have hindered progress. Here, we engineered brain and cardiac 3D bovine endothelial microvessel models that mimic the bovine brain microvasculature and the bovine aorta, respectively. By perfusing these models with two T. congolense strains, we investigated the roles of flow for parasite sequestration and tropism for different endothelial beds. We discovered that sequestration is dependent on cyclic adenosine monophosphate (cAMP) signalling, closely linked to parasite proliferation, but not associated with parasite transmission to the tsetse fly vector. Finally, by comparing the expression profiles of sequestered and non-sequestered parasites collected from a rodent model, we showed gene expression changes in sequestered parasites, including of surface variant antigens. This work presents a physiologically-relevant platform to study trypanosome interactions with the vasculature and provides a deeper understanding of the molecular and biophysical mechanisms underlying T. congolense sequestration.
      (© 2025. The Author(s).)
    • Abstract:
      Competing interests: The authors declare no competing interests.
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    • Grant Information:
      ALTF 1048-2016 European Molecular Biology Organization (EMBO); SEG #9333 European Molecular Biology Organization (EMBO); 2022.02187.PTDC Ministry of Education and Science | Fundação para a Ciência e a Tecnologia (Portuguese Science and Technology Foundation); LCF/BQ/PR23/11980034 "la Caixa" Foundation (Caixa Foundation); 771714 EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
    • Publication Date:
      Date Created: 20250226 Date Completed: 20250510 Latest Revision: 20250510
    • Publication Date:
      20260130
    • Accession Number:
      PMC11865532
    • Accession Number:
      10.1038/s42003-025-07739-z
    • Accession Number:
      40011598