Author | Gandini, Mariana | |
Author | Gras, Christopher | |
Author | Azeredo, Elzinandes Leal | |
Author | Pinto, Luzia Maria de Oliveira | |
Author | Smith, Nikaia | |
Author | Despres, Philippe | |
Author | Cunha, Rivaldo Venâncio da | |
Author | Souza, Luiz José de | |
Author | Kubelka, Claire Fernandes | |
Author | Herbeuva, Jean-Philippe | |
Access date | 2015-09-21T17:25:45Z | |
Available date | 2015-09-21T17:25:45Z | |
Document date | 2013 | pt_BR |
Citation | GANDINI, Mariana; et al. Dengue Virus Activates Membrane TRAIL Relocalization and IFN-a Production by Human Plasmacytoid Dendritic Cells In Vitro and In Vivo. PLoS Negl Trop Dis, v.7, n.6, e2257, 14p, June 2013. | pt_BR |
ISSN | 10.1371/journal.pntd.0002257 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/11773 | |
Language | eng | pt_BR |
Publisher | Plos One | pt_BR |
Rights | open access | pt_BR |
Title | Dengue Virus Activates Membrane TRAIL Relocalization and IFN-a Production by Human Plasmacytoid Dendritic Cells In Vitro and In Vivo | pt_BR |
Type | Article | pt_BR |
Abstract | Background: Dengue displays a broad spectrum of clinical manifestations that may vary from asymptomatic to severe and
even fatal features. Plasma leakage/hemorrhages can be caused by a cytokine storm induced by monocytes and dendritic
cells during dengue virus (DENV) replication. Plasmacytoid dendritic cells (pDCs) are innate immune cells and in response to
virus exposure secrete IFN-a and express membrane TRAIL (mTRAIL). We aimed to characterize pDC activation in dengue
patients and their function under DENV-2 stimulation in vitro.
Methods & Findings: Flow cytometry analysis (FCA) revealed that pDCs of mild dengue patients exhibit significantly higher
frequencies of mTRAIL compared to severe cases or healthy controls. Plasma levels of IFN-a and soluble TRAIL are increased
in mild compared to severe dengue patients, positively correlating with pDC activation. FCA experiments showed that in
vitro exposure to DENV-2 induced mTRAIL expression on pDC. Furthermore, three dimension microscopy highlighted that
TRAIL was relocalized from intracellular compartment to plasma membrane. Chloroquine treatment inhibited DENV-2-
induced mTRAIL relocalization and IFN-a production by pDC. Endosomal viral degradation blockade by chloroquine allowed
viral antigens detection inside pDCs. All those data are in favor of endocytosis pathway activation by DENV-2 in pDC.
Coculture of pDC/DENV-2-infected monocytes revealed a dramatic decrease of antigen detection by FCA. This viral antigens
reduction in monocytes was also observed after exogenous IFN-a treatment. Thus, pDC effect on viral load reduction was
mainly dependent on IFN-a production
Conclusions: This investigation characterizes, during DENV-2 infection, activation of pDCs in vivo and their antiviral role in
vitro. Thus, we propose TRAIL-expressing pDCs may have an important role in the outcome of disease. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Université Paris Descartes. CNRS UMR 8147. Paris, Frrance. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Université Paris Descartes. CNRS UMR 8601. Chimie et Biologie, Nucléo(s)tides et Immunologie Thérapeutique (CBNIT). Paris, France. | pt_BR |
Affilliation | Institut Pasteur. Unité des Interactions moléculaires Flavivirus-Hôtes. Paris, France | pt_BR |
Affilliation | Universidade Federal do Mato Grosso do Sul. Faculdade de Medicina. Departamento de Clínica Medica. Campo Grande, MS, Brasil. | pt_BR |
Affilliation | Centro de Referencia em Dengue.Campos de Goytacases, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Université Paris Descartes. CNRS UMR 8601. Chimie et Biologie, Nucléo(s)tides et Immunologie Thérapeutique (CBNIT). Paris, France. | pt_BR |
Subject | Dengue | pt_BR |
Subject | Plasmacytoid Dendritic Cells | pt_BR |
Subject | In Vitro | pt_BR |
Subject | Monocites | pt_BR |
DeCS | Dengue | pt_BR |
DeCS | Células Dendríticas | pt_BR |
DeCS | Técnicas In Vitro | pt_BR |
DeCS | Monócitos | pt_BR |