Proteomics

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

ABSTRACT: Extracellular vesicles are major components of circulating plasma holding insights into pathological processes. Here, we demonstrate high levels of EVs in plasma from patients with Plasmodium vivax (PvEVs), the most widely distributed human malaria parasite. Moreover, mass spectrometry analysis identified parasite proteins in PvEVs and their in vivo distribution demonstrated major spleen tropism. PvEVs were preferentially taken up by human spleen fibroblasts (hSFs) and this uptake induced specific and dose-dependent upregulation of ICAM-1 associated with the translocation of NF-kB to the nucleus. After activation of hSFs by PvEVs, P. vivax-infected reticulocytes from patients showed specific adhesion properties reversed by inhibiting NF-kB translocation to the nucleus. Together, these data provide novel 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

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human) Plasmodium Vivax

TISSUE(S): Blood Plasma, Extracellular Vesicle

DISEASE(S): Malaria

SUBMITTER: Eva Borràs  

LAB HEAD: Eduard Sabido

PROVIDER: PXD018337 | Pride | 2020-06-08

REPOSITORIES: Pride

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Publications

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

Toda Haruka H   Diaz-Varela Miriam M   Segui-Barber Joan J   Roobsoong Wanlapa W   Baro Barbara B   Garcia-Silva Susana S   Galiano Alicia A   Gualdrón-López Melisa M   Almeida Anne C G ACG   Brito Marcelo A M MAM   de Melo Gisely Cardoso GC   Aparici-Herraiz Iris I   Castro-Cavadía Carlos C   Monteiro Wuelton Marcelo WM   Borràs Eva E   Sabidó Eduard E   Almeida Igor C IC   Chojnacki Jakub J   Martinez-Picado Javier J   Calvo Maria M   Armengol Pilar P   Carmona-Fonseca Jaime J   Yasnot Maria Fernanda MF   Lauzurica Ricardo R   Marcilla Antonio A   Peinado Hector H   Galinski Mary R MR   Lacerda Marcus V G MVG   Sattabongkot Jetsumon J   Fernandez-Becerra Carmen C   Del Portillo Hernando A HA  

Nature communications 20200602 1

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 upta  ...[more]