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

dc.creatorTrugilho, Monique Ramos de Oliveira
dc.creatorHottz, Eugenio Damaceno
dc.creatorBrunoro, Giselle Villa Flor
dc.creatorTeixeira-Ferreira, André
dc.creatorCarvalho, Paulo Costa
dc.creatorSalazar, Gustavo Adolfo
dc.creatorZimmerman, Guy A.
dc.creatorBozza, Fernando A.
dc.creatorBozza, Patrícia Torres
dc.creatorPerales, Jonas
dc.date2017-07-13T17:33:00Z
dc.date2017-07-13T17:33:00Z
dc.date2017
dc.date.accessioned2023-09-26T23:45:54Z
dc.date.available2023-09-26T23:45:54Z
dc.identifierTRUGILHO, Monique Ramos de Oliveira et al. Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue. PLoS Pathogens, v. 13, n. 5, p. 1-27, May 2017.
dc.identifier1553-7366
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/20082
dc.identifier10.1371/journal.ppat.1006385
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8893970
dc.descriptionDengue 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectDengue
dc.subjectAtivação plaquetária
dc.subjectImmunoregulation
dc.subjectProteoma
dc.subjectDengue
dc.subjectPlatelet proteome
dc.subjectImmunoregulation
dc.subjectPlatelet activation
dc.titlePlatelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue
dc.typeArticle


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