Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence

Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence

Fecha de publicación online: 02/06/2020 Fecha de publicación en papel: 2 Junio 2020 Revista: Nature Communications

Abstract:

Plasmodium vivax is the most widely distributed human malaria parasite. Previous studies have shown that circulating microparticles during P. vivax acute attacks are indirectly associated with severity. Extracellular vesicles (EVs) are therefore major components of circulating plasma holding insights into pathological processes. Here, we demonstrate that plasma-derived EVs from Plasmodium vivax patients (PvEVs) are preferentially uptaken by human spleen fibroblasts (hSFs) as compared to the uptake of EVs from healthy individuals. Moreover, this uptake induces specific upregulation of ICAM-1 associated with the translocation of NF-kB to the nucleus. After this uptake, P. vivax-infected reticulocytes obtained from patients show specific adhesion properties to hSFs, reversed by inhibiting NF-kB translocation to the nucleus. Together, these data provide physiological EV-based insights into the mechanisms of human malaria pathology and support the existence of P. vivax-adherent parasite subpopulations in the microvasculature of the human spleen.

Autores: Toda H, Diaz-Varela M, Segui-Barber J, Roobsoong W, Baro B, Garcia-Silva S, Galiano A, Gualdrón-López M, Almeida ACG, Brito MAM, Cardoso de Melo G, Aparici-Herraiz I, Castro-Cavadía C, Monteiro WM, Borras E, Sabido E, Almeida IC, Chojnacki J, Martinez-Picado J, Calvo M, Armengol P, Carmona-Fonseca J, Yasnot MF, Lauzurica R, Marcilla A, Peinado H, Galinski MR, Lacerda MVG, Sattabongkot J, Fernandez-Becerra C, del Portillo HA

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