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- Title
Host-parasite interactions in cryptic erythrocytic infections of Plasmodium vivax malaria.
- Authors
Ayllon-Hermida, Alberto; Nicolau-Fernández, Marc; del Portillo, Hernando A.; Fernández-Becerra, Carmen
- Abstract
Introduction: The spleen and bone marrow have recently emerged as cryptic erythrocytic niches of natural Plasmodium vivax infections where the largest parasite biomass is hidden, previously P. vivax spleen-dependent genes were associated with cytoadhesion and bone marrow dyserythropoiesis induction. Last, we have shown that circulating extracellular vesicles contain parasite proteins, and act as intercellular communicators facilitating cytoadherence of infected reticulocytes to human spleen fibroblasts. The aim was functionally characterized parasite genes whose expression is dependent on an intact spleen as well as genes upregulated in the bone marrow to try unveiling the role of extracellular vesicles. Methods: We select a list of spleen-dependent genes based on global transcriptional analysis in experimental monkey infections. Moreover, RNAseq analysis of bone marrow samples revealed a list of P. vivax-genes preferentially expressed in this tissue. Due to the lack of in vitro culture system for P. vivax, we are generating transgeniclines of P. falciparum expressing selected genes using CRISPR-Cas9 technology. Results: Expression of a hypothetical spleen-dependent gene was confirmed by protein expression and confocal microscopy. In addition, extracellular vesicles from patients facilitated the binding of such transgenic line to human spleen fibroblasts. Last, to study the role of extracellular vesicles as intercellular communicators, we performed single-cell transcriptomics of human spleen fibroblasts and CD34+ cells after uptake of plasma-derived extracellular vesicles from P. vivax patients. Conclusions: This study will enable us to gain better understanding about the physiopathology and the parasite's tropism towards these reticulocyte-rich tissues. Studies on the role of extracellular vesicles in these tissues will also unveil molecular insights on the formation of these cryptic erythrocytic niches.
- Subjects
PLASMODIUM vivax; EXTRACELLULAR vesicles; BONE marrow; TRYPANOSOMA; GENE expression; BABESIA; MALARIA
- Publication
Biomédica: Revista del Instituto Nacional de Salud, 2022, Vol 42, p46
- ISSN
0120-4157
- Publication type
Article