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

• Published in: Nature communications Vol. 11; no. 1; p. 2761
• Main Authors: Toda, Haruka, Diaz-Varela, Miriam, Segui-Barber, Joan, Roobsoong, Wanlapa, Baro, Barbara, Garcia-Silva, Susana, Galiano, Alicia, Gualdrón-López, Melisa, Almeida, Anne C. G., Brito, Marcelo A. M., de Melo, Gisely Cardoso, Aparici-Herraiz, Iris, Castro-Cavadía, Carlos, Monteiro, Wuelton Marcelo, Borràs, Eva, Sabidó, Eduard, Almeida, Igor C., Chojnacki, Jakub, Martinez-Picado, Javier, Calvo, Maria, Armengol, Pilar, Carmona-Fonseca, Jaime, Yasnot, Maria Fernanda, Lauzurica, Ricardo, Marcilla, Antonio, Peinado, Hector, Galinski, Mary R., Lacerda, Marcus V. G., Sattabongkot, Jetsumon, Fernandez-Becerra, Carmen, del Portillo, Hernando A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-06-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/31; 14/19; 14/34; 14/5; 38/77; 631/1647/2067; 631/1647/245/2225; 631/326/417/2546; 64/60; 82/16; 82/58; 82/83; Animals; Cell Adhesion; Cell-Derived Microparticles; Disease Models, Animal; Extracellular vesicles; Extracellular Vesicles - metabolism; Extracellular Vesicles - parasitology; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Host-Parasite Interactions - physiology; Humanities and Social Sciences; Humans; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - metabolism; Malaria; Malaria, Vivax - parasitology; Male; Mice; Mice, Inbred C57BL; Microparticles; Microvasculature; Microvessels - parasitology; multidisciplinary; NF-kappa B - metabolism; NF-κB protein; Parasites; Pathogenesis; Plasma; Plasmodium vivax; Plasmodium vivax - physiology; Proteomics; Reticulocytes; Reticulocytes - metabolism; Reticulocytes - parasitology; Science; Science (multidisciplinary); Spleen; Spleen - metabolism; Spleen - pathology; Subpopulations; Translocation; Vector-borne diseases; Vesicles
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16337-y

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 (
Pv
EVs) are preferentially uptaken by human spleen fibroblasts (
h
SFs) 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
h
SFs, 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.
Extracellular vesicles (EVs) in plasma can affect pathogenesis of parasites, but details remain unclear. Here, Toda et al. characterize plasma-derived EVs from
Plasmodium vivax
patients and show that
Pv
EVs are preferentially taken up by human spleen fibroblasts, facilitating parasite cytoadherence.