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Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue

Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important...

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Autores principales: Trugilho, Monique Ramos de Oliveira, Hottz, Eugenio Damaceno, Brunoro, Giselle Villa Flor, Teixeira-Ferreira, André, Carvalho, Paulo Costa, Salazar, Gustavo Adolfo, Zimmerman, Guy A., Bozza, Fernando A., Bozza, Patrícia T., Perales, Jonas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453622/
https://www.ncbi.nlm.nih.gov/pubmed/28542641
http://dx.doi.org/10.1371/journal.ppat.1006385
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author Trugilho, Monique Ramos de Oliveira
Hottz, Eugenio Damaceno
Brunoro, Giselle Villa Flor
Teixeira-Ferreira, André
Carvalho, Paulo Costa
Salazar, Gustavo Adolfo
Zimmerman, Guy A.
Bozza, Fernando A.
Bozza, Patrícia T.
Perales, Jonas
author_facet Trugilho, Monique Ramos de Oliveira
Hottz, Eugenio Damaceno
Brunoro, Giselle Villa Flor
Teixeira-Ferreira, André
Carvalho, Paulo Costa
Salazar, Gustavo Adolfo
Zimmerman, Guy A.
Bozza, Fernando A.
Bozza, Patrícia T.
Perales, Jonas
author_sort Trugilho, Monique Ramos de Oliveira
collection PubMed
description Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue, and sheds light on new mechanisms of platelet activation and platelet-mediated immune and inflammatory responses.
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spelling pubmed-54536222017-06-09 Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue Trugilho, Monique Ramos de Oliveira Hottz, Eugenio Damaceno Brunoro, Giselle Villa Flor Teixeira-Ferreira, André Carvalho, Paulo Costa Salazar, Gustavo Adolfo Zimmerman, Guy A. Bozza, Fernando A. Bozza, Patrícia T. Perales, Jonas PLoS Pathog Research Article Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue, and sheds light on new mechanisms of platelet activation and platelet-mediated immune and inflammatory responses. Public Library of Science 2017-05-19 /pmc/articles/PMC5453622/ /pubmed/28542641 http://dx.doi.org/10.1371/journal.ppat.1006385 Text en © 2017 Trugilho et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Trugilho, Monique Ramos de Oliveira
Hottz, Eugenio Damaceno
Brunoro, Giselle Villa Flor
Teixeira-Ferreira, André
Carvalho, Paulo Costa
Salazar, Gustavo Adolfo
Zimmerman, Guy A.
Bozza, Fernando A.
Bozza, Patrícia T.
Perales, Jonas
Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue
title Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue
title_full Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue
title_fullStr Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue
title_full_unstemmed Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue
title_short Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue
title_sort platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453622/
https://www.ncbi.nlm.nih.gov/pubmed/28542641
http://dx.doi.org/10.1371/journal.ppat.1006385
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