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

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• dc.contributor.author Toda, Haruka
• dc.contributor.author Borràs, Eva
• dc.contributor.author Sabidó Aguadé, Eduard, 1981-
• dc.contributor.author del Portillo, Hernando A.
• dc.date.accessioned 2020-10-16T06:33:54Z
• dc.date.available 2020-10-16T06:33:54Z
• dc.date.issued 2020
• dc.description.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.
• dc.description.sponsorship We also thank the Advanced Light Microscopy Unit at the Centre for Genomic Regulation (CRG, Barcelona, Spain) for access to the Leica STED microscope. H.T. (2017FI_B1_00202) and M.D.V. (2017FI_B2_00029) are predoctoral fellows supported by Secretaria d’Universitats i Recerca del Departament d’Economia iCreixement, Generalitat de Catalunya. M.G.L. is a postdoctoral fellow supported by the Plan Estratégico (PERIS) of the Generalitat de Catalunya. I.A.H. is a predoctoral fellow supported by the Ministerio de Economia y Competitividad (FPI BES-2017081657). J.C. is supported by European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 793830. MSP3 and PHIST antibodies were generated with funding from NIH to M.R.G. (RO1A124710 and RO1AI0555994). The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I+D+i 2013–2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. We acknowledge support from the Spanish Ministry of Science, Innovation and Universities, “Centro de Excelencia Severo Ochoa 2013–2017”, SEV-2012-0208, and “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595). This research is part of ISGlobal’s Programme on the Molecular Mechanisms of Malaria which is partially supported by the Fundación Ramón Areces. Work in the laboratory of Carmen Fernandez-Becerra and Hernando A del Portillo is funded by the Ministerio Español de Economía y Competitividad (SAF2016-80655-R).
• dc.format.mimetype application/pdf
• dc.identifier.citation Toda H, Diaz-Varela M, Segui-Barber J, Roobsoong W, Baro B, Garcia-Silva S et al. Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence. Nat Commun. 2020; 11(1):2761. DOI: 10.1038/s41467-020-16337-y
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-020-16337-y
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/45495
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Commun. 2020; 11(1):2761
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/793830
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80655-R
• dc.rights © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Fluorescence imaging
• dc.subject.keyword Parasite host response
• dc.subject.keyword Proteomic analysis
• dc.title Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion