Dengue virus activates membrane TRAIL relocalization and IFN-α production by human plasmacytoid dendritic cells in vitro and in vivo.
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 dendri...
Published in: | PLoS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:6b283bf8cd6240cd8608fa6705d27ae4 2023-05-15T15:12:27+02:00 Dengue virus activates membrane TRAIL relocalization and IFN-α production by human plasmacytoid dendritic cells in vitro and in vivo. Mariana Gandini Christophe Gras Elzinandes Leal Azeredo Luzia Maria de Oliveira Pinto Nikaïa Smith Philippe Despres Rivaldo Venâncio da Cunha Luiz José de Souza Claire Fernandes Kubelka Jean-Philippe Herbeuval 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002257 https://doaj.org/article/6b283bf8cd6240cd8608fa6705d27ae4 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3675005?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0002257 https://doaj.org/article/6b283bf8cd6240cd8608fa6705d27ae4 PLoS Neglected Tropical Diseases, Vol 7, Iss 6, p e2257 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002257 2022-12-31T14:28:56Z 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-α 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-α 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-α 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-α treatment. Thus, pDC effect on viral load reduction was mainly dependent on IFN-α 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 6 e2257 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Mariana Gandini Christophe Gras Elzinandes Leal Azeredo Luzia Maria de Oliveira Pinto Nikaïa Smith Philippe Despres Rivaldo Venâncio da Cunha Luiz José de Souza Claire Fernandes Kubelka Jean-Philippe Herbeuval Dengue virus activates membrane TRAIL relocalization and IFN-α production by human plasmacytoid dendritic cells in vitro and in vivo. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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-α 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-α 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-α 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-α treatment. Thus, pDC effect on viral load reduction was mainly dependent on IFN-α 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. |
format |
Article in Journal/Newspaper |
author |
Mariana Gandini Christophe Gras Elzinandes Leal Azeredo Luzia Maria de Oliveira Pinto Nikaïa Smith Philippe Despres Rivaldo Venâncio da Cunha Luiz José de Souza Claire Fernandes Kubelka Jean-Philippe Herbeuval |
author_facet |
Mariana Gandini Christophe Gras Elzinandes Leal Azeredo Luzia Maria de Oliveira Pinto Nikaïa Smith Philippe Despres Rivaldo Venâncio da Cunha Luiz José de Souza Claire Fernandes Kubelka Jean-Philippe Herbeuval |
author_sort |
Mariana Gandini |
title |
Dengue virus activates membrane TRAIL relocalization and IFN-α production by human plasmacytoid dendritic cells in vitro and in vivo. |
title_short |
Dengue virus activates membrane TRAIL relocalization and IFN-α production by human plasmacytoid dendritic cells in vitro and in vivo. |
title_full |
Dengue virus activates membrane TRAIL relocalization and IFN-α production by human plasmacytoid dendritic cells in vitro and in vivo. |
title_fullStr |
Dengue virus activates membrane TRAIL relocalization and IFN-α production by human plasmacytoid dendritic cells in vitro and in vivo. |
title_full_unstemmed |
Dengue virus activates membrane TRAIL relocalization and IFN-α production by human plasmacytoid dendritic cells in vitro and in vivo. |
title_sort |
dengue virus activates membrane trail relocalization and ifn-α production by human plasmacytoid dendritic cells in vitro and in vivo. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002257 https://doaj.org/article/6b283bf8cd6240cd8608fa6705d27ae4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 6, p e2257 (2013) |
op_relation |
http://europepmc.org/articles/PMC3675005?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0002257 https://doaj.org/article/6b283bf8cd6240cd8608fa6705d27ae4 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002257 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
7 |
container_issue |
6 |
container_start_page |
e2257 |
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1766343122740051968 |