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

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      1 , 1 , 1 , 2 , 3 , 20 , 4 , 5 , 6 , 3 , 7 , 3 , 7 , 3 , 7 , 1 , 8 , 3 , 7 , 9 , 10 , 9 , 10 , 11 , 12 , 6 , 12 , 13 , 14 , 15 , 6 , 8 , 16 , 17 , 5 , 4 , 18 , 3 , 19 , 2 , 1 , 6 , , 1 , 6 , 14 ,
      Nature Communications
      Nature Publishing Group UK
      Fluorescence imaging, Proteomic analysis, Parasite host response

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          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.

          Abstract

          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 PvEVs are preferentially taken up by human spleen fibroblasts, facilitating parasite cytoadherence.

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          Most cited references33

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          Human malaria parasites in continuous culture.

          Plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen (1 or 5 percent). The original parasite material, derived from an infected Aotus trivirgatus monkey, was diluted more than 100 million times by the addition of human erythrocytes at 3- or 4-day intervals. The parasites continued to reproduce in their normal asexual cycle of approximately 48 hours but were no longer highly synchronous. The have remained infective to Aotus.
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            FunRich: An open access standalone functional enrichment and interaction network analysis tool.

            As high-throughput techniques including proteomics become more accessible to individual laboratories, there is an urgent need for a user-friendly bioinformatics analysis system. Here, we describe FunRich, an open access, standalone functional enrichment and network analysis tool. FunRich is designed to be used by biologists with minimal or no support from computational and database experts. Using FunRich, users can perform functional enrichment analysis on background databases that are integrated from heterogeneous genomic and proteomic resources (>1.5 million annotations). Besides default human specific FunRich database, users can download data from the UniProt database, which currently supports 20 different taxonomies against which enrichment analysis can be performed. Moreover, the users can build their own custom databases and perform the enrichment analysis irrespective of organism. In addition to proteomics datasets, the custom database allows for the tool to be used for genomics, lipidomics and metabolomics datasets. Thus, FunRich allows for complete database customization and thereby permits for the tool to be exploited as a skeleton for enrichment analysis irrespective of the data type or organism used. FunRich (http://www.funrich.org) is user-friendly and provides graphical representation (Venn, pie charts, bar graphs, column, heatmap and doughnuts) of the data with customizable font, scale and color (publication quality).
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              Vesiclepedia 2019: a compendium of RNA, proteins, lipids and metabolites in extracellular vesicles

              Abstract Extracellular vesicles (EVs) are membranous vesicles that are released by both prokaryotic and eukaryotic cells into the extracellular microenvironment. EVs can be categorised as exosomes, ectosomes or shedding microvesicles and apoptotic bodies based on the mode of biogenesis. EVs contain biologically active cargo of nucleic acids, proteins, lipids and metabolites that can be altered based on the precise state of the cell. Vesiclepedia (http://www.microvesicles.org) is a web-based compendium of RNA, proteins, lipids and metabolites that are identified in EVs from both published and unpublished studies. Currently, Vesiclepedia contains data obtained from 1254 EV studies, 38 146 RNA entries, 349 988 protein entries and 639 lipid/metabolite entries. Vesiclepedia is publicly available and allows users to query and download EV cargo based on different search criteria. The mode of EV isolation and characterization, the biophysical and molecular properties and EV-METRIC are listed in the database aiding biomedical scientists in assessing the quality of the EV preparation and the corresponding data obtained. In addition, FunRich-based Vesiclepedia plugin is incorporated aiding users in data analysis.
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                Author and article information

                Contributors
                carmen.fernandez@isglobal.org
                hernandoa.delportillo@isglobal.org
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                2 June 2020
                2 June 2020
                2020
                : 11
                : 2761
                Affiliations
                [1 ]ISNI 0000 0000 9635 9413, GRID grid.410458.c, ISGlobal, Hospital Clínic - Universitat de Barcelona, ; Barcelona, 08036 Spain
                [2 ]ISNI 0000 0004 1937 0490, GRID grid.10223.32, Mahidol Vivax Research Unit, Faculty of Tropical Medicine, , Mahidol University, ; Bangkok, 10400 Thailand
                [3 ]ISNI 0000 0004 0486 0972, GRID grid.418153.a, Fundaçao de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), ; Manaus, Amazonas 69040-000 Brazil
                [4 ]ISNI 0000 0000 8700 1153, GRID grid.7719.8, Microenvironment and Metastasis Laboratory, Department of Molecular Oncology, , Spanish National Cancer Research Center (CNIO), ; Madrid, 28029 Spain
                [5 ]ISNI 0000 0001 2173 938X, GRID grid.5338.d, Àrea de Parasitologia, Departament de Farmàcia i Tecnologia Farmacèutica i Parasitologia, , Universitat de València, ; Burjassot, Valencia 46100 Spain
                [6 ]GRID grid.429186.0, Germans Trias i Pujol Health Science Research Institute (IGTP), ; Badalona, 08916 Spain
                [7 ]ISNI 0000 0000 8024 0602, GRID grid.412290.c, Universidade do Estado do Amazonas (UEA), ; Manaus, Amazonas 69020-070 Brazil
                [8 ]ISNI 0000 0000 8882 5269, GRID grid.412881.6, Grupo de Salud y Comunidad Cesar Uribe Piedrahíta, , Universidad de Antioquia, ; Medellín, Colombia
                [9 ]GRID grid.473715.3, Proteomics Unit, Centre de Regulació Genòmica (CRG), , Barcelona Institute of Science and Technology (BIST), ; Barcelona, 08003 Spain
                [10 ]ISNI 0000 0001 2172 2676, GRID grid.5612.0, Universitat Pompeu Fabra (UPF), ; Barcelona, 08002 Spain
                [11 ]ISNI 0000 0001 0668 0420, GRID grid.267324.6, Border Biomedical Research Center, Department of Biological Sciences, College of Science, , University of Texas El Paso, ; El Paso, TX 79902 USA
                [12 ]AIDS Research Institute IrsiCaixa, Badalona, 08916 Spain
                [13 ]GRID grid.440820.a, University of Vic-Central University of Catalonia, ; Vic, 08500 Spain
                [14 ]ISNI 0000 0000 9601 989X, GRID grid.425902.8, Institució Catalana de Recerca i Estudis Avançats (ICREA), ; Barcelona, 08010 Spain
                [15 ]ISNI 0000 0004 1937 0247, GRID grid.5841.8, Unitat de Microscopia Òptica Avançada, Facultat de Medicina, Centres Científics i Tecnològics, , Universitat de Barcelona, ; Barcelona, 08028 Spain
                [16 ]ISNI 0000 0004 0486 6602, GRID grid.441929.3, Grupo de Investigaciones Microbiológicas y Biomédicas de Córdoba-GIMBIC, , Universidad de Córdoba, ; Monteria, 230001 Colombia
                [17 ]ISNI 0000 0004 1767 6330, GRID grid.411438.b, Nephrology Service, , Germans Trias i Pujol University Hospital, ; Badalona, 08916 Spain
                [18 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Emory Vaccine Center, Yerkes National Primate Research Center, School of Medicine, Division of Infectious Diseases, , Emory University, ; Atlanta, GA 30329 USA
                [19 ]ISNI 0000 0001 0723 0931, GRID grid.418068.3, Instituto Leônidas & Maria Deane (ILMD), Fiocruz, ; Manaus, Amazonas 69057-070 Brazil
                [20 ]ISNI 0000 0000 9635 9413, GRID grid.410458.c, Present Address: ISGlobal, Hospital Clínic - Universitat de Barcelona, ; Barcelona, Spain
                Author information
                http://orcid.org/0000-0002-8753-8115
                http://orcid.org/0000-0001-6272-2808
                http://orcid.org/0000-0002-1789-0439
                http://orcid.org/0000-0003-1065-0245
                http://orcid.org/0000-0002-8202-6751
                http://orcid.org/0000-0001-5100-7809
                http://orcid.org/0000-0002-4457-8096
                http://orcid.org/0000-0002-7473-0474
                http://orcid.org/0000-0003-0004-0531
                http://orcid.org/0000-0002-4256-3413
                http://orcid.org/0000-0001-5154-0013
                http://orcid.org/0000-0002-5278-3452
                Article
                16337
                10.1038/s41467-020-16337-y
                7265481
                32487994
                f106a3bb-7488-493f-8c52-720a48962c1a
                © 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/.

                History
                : 30 June 2019
                : 25 April 2020
                Funding
                Funded by: Secretaria d’Universitats i Recerca del Departament d’Economia iCreixement, Generalitat de Catalunya (2017FI_B1_00202)
                Funded by: Fundación Ramón Areces, 2014. “Investigación en Ciencias de la Vida y de la Materia”, Project “Exosomas: Nuevos comunicadores intercelulares y su aplicabilidad como agentes terapéuticos en enfermedades parasitarias desatendidas”.
                Funded by: Plan Estratégico (PERIS) of the Generalitat de Catalunya
                Funded by: Ministerio de Economia y Competitividad (FPI BES-2017081)
                Funded by: 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.
                Funded by: European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 793830.
                Funded by: NIH (RO1A124710 and RO1AI0555994)
                Funded by: Ministerio Español de Economía y Competitividad (SAF2016-80655-R) and by the Network of Excellency in Research and Innovation on Exosomes (REDiEX) (SAF2015-71231-REDT) and 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). ISGlobal and IGTP are members of the CERCA Programme, Generalitat de Catalunya. This work received specific support from the Fundación Ramón Areces, 2014. “Investigación en Ciencias de la Vida y de la Materia”, Project “Exosomas: Nuevos comunicadores intercelulares y su aplicabilidad como agentes terapéuticos en enfermedades parasitarias desatendidas”.
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                © The Author(s) 2020

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                fluorescence imaging,proteomic analysis,parasite host response
                Uncategorized
                fluorescence imaging, proteomic analysis, parasite host response

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