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PERIPHERAL ORGANS OF DENGUE FATAL CASES PRESENT STRONG PRO-INFLAMMATORY RESPONSE WITH PARTICIPATION OF IFN-GAMMA-, TNF-ALPHA- AND RANTES-PRODUCING CELLS
Dengue
Casos fatais
Fator de Necrose Tumoral alfa
Quimiocina CCL5
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Laboratório de Modelagem Molecular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Estado do Rio de Janeiro. Hospital Universitário Gaffreé Guinle. Departamento de Anatomia Patológica. Rio de Janeiro, RJ, Brasil.
Ohio State University Comprehensive Cancer Center. Columbus, Ohio, USA / Phylogeny In. Powell, Ohio, USA.
Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Anatomia Patológica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Laboratório de Modelagem Molecular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Estado do Rio de Janeiro. Hospital Universitário Gaffreé Guinle. Departamento de Anatomia Patológica. Rio de Janeiro, RJ, Brasil.
Ohio State University Comprehensive Cancer Center. Columbus, Ohio, USA / Phylogeny In. Powell, Ohio, USA.
Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Anatomia Patológica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ. Brasil.
Abstract
Dengue disease is an acute viral illness caused by dengue virus (DENV) that can progress to hemorrhagic stages leading to about 20000 deaths every year worldwide. Despite many clinical investigations regarding dengue, the immunopathogenic process by which infected patients evolve to the severe forms is not fully understood. Apart from differences in virulence and the antibody cross reactivity that can potentially augment virus replication, imbalanced cellular immunity is also seen as a major concern in the establishment of severe dengue. In this context, the investigation of cellular immunity and its products in dengue fatal cases may provide valuable data to help revealing dengue immunopathogenesis. Here, based in four dengue fatal cases infected by the serotype 3 in Brazil, different peripheral organs (livers, lungs and kidneys) were studied to evaluate the presence of cell infiltrates and the patterns of local cytokine response. The overall scenario of the studied cases revealed a considerable systemic involvement of infection with mononuclear cells targeted to all of the evaluated organs, as measured by immunohistochemistry (IHC). Quantification of cytokine-expressing cells in peripheral tissues was also performed to characterize the ongoing inflammatory process by the severe stage of the disease. Increased levels of IFN-γ- and TNF-α-expressing cells in liver, lung and kidney samples of post-mortem subjects evidenced a strong pro-inflammatory induction in these tissues. The presence of increased RANTES-producing cell numbers in all analyzed organs suggested a possible link between the clinical status and altered vascular permeability. Co-staining of DENV RNA and IFN-γ or TNF-α using in situ hibridization and IHC confirmed the virus-specific trigger of the pro-inflammatory response. Taken together, this work provided additional evidences that corroborated with the traditional theories regarding the "cytokine storm" and the occurrence of uneven cellular immunity in response to DENV as major reasons for progress to severe disease.
Keywords in Portuguese
Resposta Pró-InflamatóriaDengue
Casos fatais
Fator de Necrose Tumoral alfa
Quimiocina CCL5
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