Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author WEG, Cornelia A. M. van de
PANNUTI, Claudio S. FMUSP-HC
ARAUJO, Evaldo S. A. de
HAM, Henk-Jan van den
ANDEWEG, Arno C.
BOAS, Lucy S. V. FMUSP-HC
FELIX, Alvina C.
CARVALHO, Karina I. FMUSP-HC
MATOS, Andreia M. de FMUSP-HC
LEVI, Jose E. FMUSP-HC
ROMANO, Camila M. FMUSP-HC
CENTRONE, Cristiane C.
RODRIGUES, Celia L. de Lima
LUNA, Expedito FMUSP-HC
GORP, Eric C. M. van
OSTERHAUS, Albert D. M. E.
MARTINA, Byron E. E.
KALLAS, Esper G. FMUSP-HC
dc.date.issued 2013
dc.identifier.citation PLOS NEGLECTED TROPICAL DISEASES, v.7, n.5, article ID e2236, 13p, 2013
dc.identifier.issn 1935-2735
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/1982
dc.description.abstract Background: Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection. Methods: Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of Sao Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles. Results: Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease. Conclusions: The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis.
dc.description.sponsorship · Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazilian Ministry of Science and Technology'' [CNPq] [476088/2009-7]
· CNPq
· Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazilian Ministry of Education
· Virgo consortium
· Dutch government [FES0908]
· Netherlands Genomics Initiative (NGI) [050-060-452]
dc.language.iso eng
dc.publisher PUBLIC LIBRARY SCIENCE
dc.relation.ispartof Plos Neglected Tropical Diseases
dc.rights restrictedAccess
dc.subject.other hemorrhagic-fever; bacterial lipopolysaccharide; human monocytes/macrophages; cytokine patterns; interferon-gamma; plasma leakage; shock syndrome; septic shock; tnf-alpha; expression
dc.title Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease
dc.type article
dc.rights.holder Copyright PUBLIC LIBRARY SCIENCE
dc.description.group LIM/52
dc.description.group LIM/60
dc.identifier.doi 10.1371/journal.pntd.0002236
dc.identifier.pmid 23717702
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author PANNUTI, Claudio S.:FM:MIP
hcfmusp.author BOAS, Lucy S. V.:HC:LIM/52
hcfmusp.author CARVALHO, Karina I.:FM:
hcfmusp.author MATOS, Andreia M. de:FM:
hcfmusp.author LEVI, Jose E.:HC:INCOR
hcfmusp.author ROMANO, Camila M.:HC:LIM/52
hcfmusp.author LUNA, Expedito:IMT:IMT
hcfmusp.author KALLAS, Esper G.:FM:MCM
hcfmusp.author.external · WEG, Cornelia A. M. van de:Erasmus MC, Virosci Lab, Rotterdam, Netherlands
· ARAUJO, Evaldo S. A. de:Univ Sao Paulo, Fac Med, Inst Med Trop Sao Paulo, Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias LIM 52, Sao Paulo, Brazil; Hosp Ana Costa, Dept Infect Dis, Santos, Brazil
· HAM, Henk-Jan van den:Erasmus MC, Virosci Lab, Rotterdam, Netherlands
· ANDEWEG, Arno C.:Erasmus MC, Virosci Lab, Rotterdam, Netherlands
· FELIX, Alvina C.:Univ Sao Paulo, Fac Med, Inst Med Trop Sao Paulo, Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias LIM 52, Sao Paulo, Brazil
· CENTRONE, Cristiane C.:Univ Sao Paulo, Fac Med, Inst Med Trop Sao Paulo, Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias LIM 52, Sao Paulo, Brazil
· RODRIGUES, Celia L. de Lima:Univ Sao Paulo, Fac Med, Inst Med Trop Sao Paulo, Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias LIM 52, Sao Paulo, Brazil
· GORP, Eric C. M. van:Erasmus MC, Virosci Lab, Rotterdam, Netherlands
· OSTERHAUS, Albert D. M. E.:Erasmus MC, Virosci Lab, Rotterdam, Netherlands
· MARTINA, Byron E. E.:Erasmus MC, Virosci Lab, Rotterdam, Netherlands
hcfmusp.origem.id 2-s2.0-84878485590
hcfmusp.origem.id WOS:000319994400038
hcfmusp.publisher.city SAN FRANCISCO
hcfmusp.publisher.country USA
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dc.description.index MEDLINE
hcfmusp.citation.scopus 29
hcfmusp.citation.wos 25


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