Browsing by Author "Zorrinho-Almeida, Maria"
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- Bioengineered 3D microvessels and complementary animal models reveal mechanisms of Trypanosoma congolense sequestrationPublication . Porqueddu, Teresa; Zorrinho-Almeida, Maria; Niz, Mariana De; Casas-Sánchez, Aitor; Introini, Viola; Sender, Silvia Sanz; Carrasqueira, Diana; Figueiredo, Luísa M.; Bernabeu, Maria; Pereira, Sara SilvaIn 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.
- Leveraging microphysiological systems to expedite understanding of host-parasite interactionsPublication . Zorrinho-Almeida, Maria; de-Carvalho, Jorge; Bernabeu, Maria; Pereira, Sara SilvaMicrophysiological systems (MPS) replicate the dynamic interactions between cells, tissues, and fluids. They have emerged as transformative tools for biology and have been increasingly applied to host–parasite interactions. Offering a better representation of cellular behavior compared with traditional in vitro models, MPS can facilitate the study of parasite tropism, immune evasion, and life cycle transitions across diverse parasitic diseases. Applications span multiple host tissues and pathogens, leveraging advanced bioengineering and microfabrication techniques to address long-standing knowledge gaps. Here, we review recent advances in MPS applied to parasitic diseases and identify persisting challenges and opportunities for investment. By refining these systems and integrating host multicellular models and parasites, MPS hold vast potential to revolutionize parasitology, enhancing our ability to combat parasitic diseases through deeper mechanistic understanding and targeted interventions.