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

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 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 () and Hernando A. Portillo ()
Additional contact information
Haruka Toda: ISGlobal, Hospital Clínic - Universitat de Barcelona
Miriam Diaz-Varela: ISGlobal, Hospital Clínic - Universitat de Barcelona
Joan Segui-Barber: ISGlobal, Hospital Clínic - Universitat de Barcelona
Wanlapa Roobsoong: Mahidol University
Barbara Baro: Fundaçao de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD)
Susana Garcia-Silva: Spanish National Cancer Research Center (CNIO)
Alicia Galiano: Universitat de València
Melisa Gualdrón-López: Germans Trias i Pujol Health Science Research Institute (IGTP)
Anne C. G. Almeida: Fundaçao de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD)
Marcelo A. M. Brito: Fundaçao de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD)
Gisely Cardoso Melo: Fundaçao de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD)
Iris Aparici-Herraiz: ISGlobal, Hospital Clínic - Universitat de Barcelona
Carlos Castro-Cavadía: Universidad de Antioquia
Wuelton Marcelo Monteiro: Fundaçao de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD)
Eva Borràs: Barcelona Institute of Science and Technology (BIST)
Eduard Sabidó: Barcelona Institute of Science and Technology (BIST)
Igor C. Almeida: University of Texas El Paso
Jakub Chojnacki: AIDS Research Institute IrsiCaixa
Javier Martinez-Picado: Germans Trias i Pujol Health Science Research Institute (IGTP)
Maria Calvo: Universitat de Barcelona
Pilar Armengol: Germans Trias i Pujol Health Science Research Institute (IGTP)
Jaime Carmona-Fonseca: Universidad de Antioquia
Maria Fernanda Yasnot: Universidad de Córdoba
Ricardo Lauzurica: Germans Trias i Pujol University Hospital
Antonio Marcilla: Universitat de València
Hector Peinado: Spanish National Cancer Research Center (CNIO)
Mary R. Galinski: Emory University
Marcus V. G. Lacerda: Fundaçao de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD)
Jetsumon Sattabongkot: Mahidol University
Carmen Fernandez-Becerra: ISGlobal, Hospital Clínic - Universitat de Barcelona
Hernando A. Portillo: ISGlobal, Hospital Clínic - Universitat de Barcelona

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16337-y

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