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

间日疟原虫患者血浆来源的细胞外囊泡通过NF-κB信号通路向脾脏成纤维细胞发出信号,促进寄生虫的细胞黏附。

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

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.

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