Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.

<h4>Background</h4>Deciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians.<h4>...

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Autores principales:	Stéphanie Devignot, Cédric Sapet, Veasna Duong, Aurélie Bergon, Pascal Rihet, Sivuth Ong, Patrich T Lorn, Norith Chroeung, Sina Ngeav, Hugues J Tolou, Philippe Buchy, Patricia Couissinier-Paris
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b9754cdcae94c2498c48f30d87b2fa1
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spelling	oai:doaj.org-article:7b9754cdcae94c2498c48f30d87b2fa12021-12-02T20:19:57ZGenome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.1932-620310.1371/journal.pone.0011671https://doaj.org/article/7b9754cdcae94c2498c48f30d87b2fa12010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20652028/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Deciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians.<h4>Methodology/principal findings</h4>Based on a prospective study, we analyzed the genome-wide expression profiles of whole blood cells from 48 matched Cambodian children: 19 progressed to DSS while 16 and 13 presented respectively classical dengue fever (DF) or dengue hemorrhagic fever grades I/II (DHF). Using multi-way analysis of variance (ANOVA) and adjustment of p-values to control the False Discovery Rate (FDR<10%), we identified a signature of 2959 genes differentiating DSS patients from both DF and DHF, and showed a strong association of this DSS-gene signature with the dengue disease phenotype. Using a combined approach to analyse the molecular patterns associated with the DSS-gene signature, we provide an integrative overview of the transcriptional responses altered in DSS children. In particular, we show that the transcriptome of DSS children blood cells is characterized by a decreased abundance of transcripts related to T and NK lymphocyte responses and by an increased abundance of anti-inflammatory and repair/remodeling transcripts. We also show that unexpected pro-inflammatory gene patterns at the interface between innate immunity, inflammation and host lipid metabolism, known to play pathogenic roles in acute and chronic inflammatory diseases associated with systemic vascular dysfunction, are transcriptionnally active in the blood cells of DSS children.<h4>Conclusions/significance</h4>We provide a global while non exhaustive overview of the molecular mechanisms altered in of DSS children and suggest how they may interact to lead to final vascular homeostasis breakdown. We suggest that some mechanisms identified should be considered putative therapeutic targets or biomarkers of progression to DSS.Stéphanie DevignotCédric SapetVeasna DuongAurélie BergonPascal RihetSivuth OngPatrich T LornNorith ChroeungSina NgeavHugues J TolouPhilippe BuchyPatricia Couissinier-ParisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11671 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stéphanie Devignot Cédric Sapet Veasna Duong Aurélie Bergon Pascal Rihet Sivuth Ong Patrich T Lorn Norith Chroeung Sina Ngeav Hugues J Tolou Philippe Buchy Patricia Couissinier-Paris Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.
description	<h4>Background</h4>Deciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians.<h4>Methodology/principal findings</h4>Based on a prospective study, we analyzed the genome-wide expression profiles of whole blood cells from 48 matched Cambodian children: 19 progressed to DSS while 16 and 13 presented respectively classical dengue fever (DF) or dengue hemorrhagic fever grades I/II (DHF). Using multi-way analysis of variance (ANOVA) and adjustment of p-values to control the False Discovery Rate (FDR<10%), we identified a signature of 2959 genes differentiating DSS patients from both DF and DHF, and showed a strong association of this DSS-gene signature with the dengue disease phenotype. Using a combined approach to analyse the molecular patterns associated with the DSS-gene signature, we provide an integrative overview of the transcriptional responses altered in DSS children. In particular, we show that the transcriptome of DSS children blood cells is characterized by a decreased abundance of transcripts related to T and NK lymphocyte responses and by an increased abundance of anti-inflammatory and repair/remodeling transcripts. We also show that unexpected pro-inflammatory gene patterns at the interface between innate immunity, inflammation and host lipid metabolism, known to play pathogenic roles in acute and chronic inflammatory diseases associated with systemic vascular dysfunction, are transcriptionnally active in the blood cells of DSS children.<h4>Conclusions/significance</h4>We provide a global while non exhaustive overview of the molecular mechanisms altered in of DSS children and suggest how they may interact to lead to final vascular homeostasis breakdown. We suggest that some mechanisms identified should be considered putative therapeutic targets or biomarkers of progression to DSS.
format	article
author	Stéphanie Devignot Cédric Sapet Veasna Duong Aurélie Bergon Pascal Rihet Sivuth Ong Patrich T Lorn Norith Chroeung Sina Ngeav Hugues J Tolou Philippe Buchy Patricia Couissinier-Paris
author_facet	Stéphanie Devignot Cédric Sapet Veasna Duong Aurélie Bergon Pascal Rihet Sivuth Ong Patrich T Lorn Norith Chroeung Sina Ngeav Hugues J Tolou Philippe Buchy Patricia Couissinier-Paris
author_sort	Stéphanie Devignot
title	Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.
title_short	Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.
title_full	Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.
title_fullStr	Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.
title_full_unstemmed	Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.
title_sort	genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/7b9754cdcae94c2498c48f30d87b2fa1
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Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.

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