Differential expression of Toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.

<h4>Background</h4>Dengue hemorrhagic fever (DHF) is observed in individuals that have pre-existing heterotypic dengue antibodies and is associated with increased viral load and high levels of pro-inflammatory cytokines early in infection. Interestingly, a recent study showed that dengue...

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Autores principales:	Silvia Torres, Juan Carlos Hernández, Diana Giraldo, Margarita Arboleda, Mauricio Rojas, Jolanda M Smit, Silvio Urcuqui-Inchima
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/6714dc0c70134c36b929e30602e76013
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spelling	oai:doaj.org-article:6714dc0c70134c36b929e30602e760132021-11-18T09:15:20ZDifferential expression of Toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.1935-27271935-273510.1371/journal.pntd.0002060https://doaj.org/article/6714dc0c70134c36b929e30602e760132013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23469297/pdf/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Dengue hemorrhagic fever (DHF) is observed in individuals that have pre-existing heterotypic dengue antibodies and is associated with increased viral load and high levels of pro-inflammatory cytokines early in infection. Interestingly, a recent study showed that dengue virus infection in the presence of antibodies resulted in poor stimulation of Toll-like receptors (TLRs), thereby facilitating virus particle production, and also suggesting that TLRs may contribute to disease pathogenesis.<h4>Methodology/principal findings</h4>We evaluated the expression levels of TLR2, 3, 4 and 9 and the co-stimulatory molecules CD80 and CD86 by flow cytometry. This was evaluated in monocytes, in myeloid and plasmacytoid dendritic cells (mDCs and pDCs) from 30 dengue patients with different clinical outcomes and in 20 healthy controls. Increased expression of TLR3 and TLR9 in DCs of patients with dengue fever (DF) early in infection was detected. In DCs from patients with severe manifestations, poor stimulation of TLR3 and TLR9 was observed. In addition, we found a lower expression of TLR2 in patients with DF compared to DHF. Expression levels of TLR4 were not affected. Furthermore, the expression of CD80 and CD86 was altered in mDCs and CD86 in pDCs of severe dengue cases. We show that interferon alpha production decreased in the presence of dengue virus after stimulation of PBMCs with the TLR9 agonist (CpG A). This suggests that the virus can affect the interferon response through this signaling pathway.<h4>Conclusions/significance</h4>These results show that during dengue disease progression, the expression profile of TLRs changes depending on the severity of the disease. Changes in TLRs expression could play a central role in DC activation, thereby influencing the innate immune response.Silvia TorresJuan Carlos HernándezDiana GiraldoMargarita ArboledaMauricio RojasJolanda M SmitSilvio Urcuqui-InchimaPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 7, Iss 2, p e2060 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Silvia Torres Juan Carlos Hernández Diana Giraldo Margarita Arboleda Mauricio Rojas Jolanda M Smit Silvio Urcuqui-Inchima Differential expression of Toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.
description	<h4>Background</h4>Dengue hemorrhagic fever (DHF) is observed in individuals that have pre-existing heterotypic dengue antibodies and is associated with increased viral load and high levels of pro-inflammatory cytokines early in infection. Interestingly, a recent study showed that dengue virus infection in the presence of antibodies resulted in poor stimulation of Toll-like receptors (TLRs), thereby facilitating virus particle production, and also suggesting that TLRs may contribute to disease pathogenesis.<h4>Methodology/principal findings</h4>We evaluated the expression levels of TLR2, 3, 4 and 9 and the co-stimulatory molecules CD80 and CD86 by flow cytometry. This was evaluated in monocytes, in myeloid and plasmacytoid dendritic cells (mDCs and pDCs) from 30 dengue patients with different clinical outcomes and in 20 healthy controls. Increased expression of TLR3 and TLR9 in DCs of patients with dengue fever (DF) early in infection was detected. In DCs from patients with severe manifestations, poor stimulation of TLR3 and TLR9 was observed. In addition, we found a lower expression of TLR2 in patients with DF compared to DHF. Expression levels of TLR4 were not affected. Furthermore, the expression of CD80 and CD86 was altered in mDCs and CD86 in pDCs of severe dengue cases. We show that interferon alpha production decreased in the presence of dengue virus after stimulation of PBMCs with the TLR9 agonist (CpG A). This suggests that the virus can affect the interferon response through this signaling pathway.<h4>Conclusions/significance</h4>These results show that during dengue disease progression, the expression profile of TLRs changes depending on the severity of the disease. Changes in TLRs expression could play a central role in DC activation, thereby influencing the innate immune response.
format	article
author	Silvia Torres Juan Carlos Hernández Diana Giraldo Margarita Arboleda Mauricio Rojas Jolanda M Smit Silvio Urcuqui-Inchima
author_facet	Silvia Torres Juan Carlos Hernández Diana Giraldo Margarita Arboleda Mauricio Rojas Jolanda M Smit Silvio Urcuqui-Inchima
author_sort	Silvia Torres
title	Differential expression of Toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.
title_short	Differential expression of Toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.
title_full	Differential expression of Toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.
title_fullStr	Differential expression of Toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.
title_full_unstemmed	Differential expression of Toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.
title_sort	differential expression of toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6714dc0c70134c36b929e30602e76013
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Differential expression of Toll-like receptors in dendritic cells of patients with dengue during early and late acute phases of the disease.

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