P34 - Parasitología

Role of Extracellular Vesicles from Plasmodium falciparum cultures in their interaction with BeWo Cells: implications for cytoadherence and energy profile

Fernández Rivadeneira, Eduardo¹ - Vilchez Larrea, Salomé² - Echeverry, Tomás³ - Farina, Mariana^3,4 - Alonso, Guillermo² - Schwarzbaum, Pablo¹ - Alvarez, Cora Lilia^1,5

1) IQUIFIB-CONICET
2) INGEBI-CONICET
3) CEFYBO-UBA-CONICET
4) Cátedra de Fisiología, Facultad de Odontología, UBA
5) Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, UBA.
Contacto: cerfernandez8@gmail.com

Plasmodium falciparum, the most dangerous parasitic agent causing malaria, invades human red blood cells (RBCs) and remodels them by exporting parasite-derived proteins. A key virulence factor is PfEMP1, which enables infected RBCs (iRBCs) to adhere to host tissues. In placental malaria, the VAR2CSA variant of PfEMP1 binds specifically to chondroitin sulfate A, abundantly expressed in the placental syncytiotrophoblast, leading to inflammation and poor pregnancy outcomes. Recent studies highlight the role of extracellular vesicles (EVs) as mediators of host–parasite communication. EVs released by infected red blood cells (iRBCs) transport parasite-derived proteins, including PfEMP1, and have emerged as active contributors to malaria pathogenesis.
This study aimed to characterize iRBC-derived EVs and evaluate their effects on BeWo cells, a trophoblast cell line used as a model for placental malaria research.
EVs were isolated from P. falciparum cultures (3–10% parasitemia) using ultracentrifugation. Their size and concentration were assessed by nanoparticle tracking analysis. Adhesion and energy profile were measured after incubation with iRBC-derived EVs. Adhesion was measured using a colorimetric assay, and changes in protein synthesis, a process highly dependent on ATP, were analyzed by flow cytometry.
Although EVs from infected and control RBCs cultures had a similar average diameter (~150 nm), infection produced 3.4 times more EVs. Notably, exposing control RBCs to iRBC-derived EVs increased their adhesion to BeWo cells (~20%), suggesting that EVs enhance cytoadherence, a key feature of malaria pathogenesis. Additionally, BeWo cells incubated with iRBC-derived EVs obtained their energy primarily from glycolysis.
In conclusion, iRBC-derived EVs increase adhesiveness to trophoblast cells and shift their metabolism toward glycolysis. This reprogramming may reflect increased energy demands linked to trophoblast activation. We hypothesize that such activation promotes pro-inflammatory cytokine release, potentially impairing syncytiotrophoblast function and maternofetal exchange. While this mechanism remains to be tested, it provides a compelling basis for future investigation.

Palabras clave: PLASMODIUM FALCIPARUM, EXTRACELLULAR VESICLES (EVS), ADHESION, TROPHOBLAST