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

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art_PANNUTI_Microbial_Translocation_Is_Associated_with_Extensive_Immune_Activation_2013.PDF (771.3 KB)
Citações na Scopus
66
Tipo de produção
article
Data de publicação
2013
Editora
PUBLIC LIBRARY SCIENCE
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
WEG, Cornelia A. M. van de
ARAUJO, Evaldo S. A. de
HAM, Henk-Jan van den
ANDEWEG, Arno C.
FELIX, Alvina C.
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
PLOS NEGLECTED TROPICAL DISEASES, v.7, n.5, article ID e2236, 13p, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
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URI
https://observatorio.fm.usp.br/handle/OPI/1982
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MIP
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - LIM/52
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