Multi-organ involvement in dengue is mediated by prominent T-cell and monocyte-macrophages responses
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1
Universidad del Valle, Department of Microbiology, Colombia
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2
RED AEDES: Abordando Áreas Endémicas del Dengue para la Disminución de su Impacto en la Sociedad", Colombia
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3
Johns Hopkins School of Medicine, Department of Neurology, United States
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4
Universidad del Valle, Department of Pathology, Colombia
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5
Universidad Industrial de Santander, Department of Pathology, Colombia
Dengue is the most common arthropod borne infectious disease worldwide. The spectrum of disease is broad and most cases result in mild illness but some patients develop severe symptoms such as hemorrhagic manifestations, fluid leakage and organ failure. Increasing evidence suggests that the severe manifestations of dengue are immunopathologically mediated. Cardiac, hepatic or neurological complications are frequent in severe dengue. Although the early onset of enhanced inflammation upon the secondary infection may explain endothelial dysfunction and plasma leakage leading to the circulatory failure in cases of severe dengue, there is a lack of understanding of dengue pathogenesis in target organs. To examine the extent of the immunopathological mechanisms in complicated dengue, we studied 11 fatal dengue autopsy cases in a hyperendemic region southwest of Colombia between 2009 and 2013. The pathological changes were examined in tissue samples which included brain, heart, kidney, liver, lung, lymph nodes and spleen. Standard histological techniques as well as immunostaining for T cells (CD3), B cells (CD20), and monocyte-macrophages (CD68) markers were used to characterize cellular immune processes. The presence of dengue virus antigen (envelope E antigen) was also examined by immunocytochemistry. All cases exhibited prominent inflammation and tissue damage. Although, the extent of organ involvement was variable within or between cases, liver and lungs were the most frequently affected organs in which vascular congestion, hemorrhagic changes and inflammation were prominent. A frequent feature was acute hepatitis and necrosis. Abundant macro and microsteatosis were also present. Portal space Inflammation was characterized by infiltration of T cells and macrophages. Dengue virus antigen was observed mostly in macrophages. Lung pathology was characterized by alveolar hemorrhage, diffuse alveolar damage, hyaline membrane formation and septal thickening, the alveolar septum also showed abundant mononuclear infiltration that was predominantly comprised of T cells and macrophages. An increase in the number of macrophages was also observed in cardiac tissue. Few cases showed renal interstitial hemorrhage, vascular congestion, and acute tubular necrosis and only in one case inflammatory changes were present. Lymph nodes showed follicular lymphoid hyperplasia with dilatation of sinusoids and a few dengue positive cells in the subcapsular sinus. None of the cases showed significant brain pathology with exception of mild leptomeningeal lymphocyte infiltrate was found in some cases, although the extent of examination was limited to few brain regions. These results confirm the role of the immune response to dengue virus in the tissue damage associated with fatal dengue and highlights the participation of T-cells and monocyte-macrophage immune mediated responses in the viral-induced organ pathology. This data also unveiled a dengue virus-induced lung injury that was not described previously.
Acknowledgements
This work is funding by Sistema General de Regalias of Colombia, Universidad Industrial de Santander and Universidad del Valle.
Keywords:
Dengue infection,
immunopathology,
target organ damage,
Severe Dengue,
pathogenesis of dengue
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Poster Presentation
Topic:
Infectious and parasitic diseases
Citation:
Gonzalez-Cardona
JJ,
Pardo
CA,
Vargas
DA,
Mantilla
JC,
Parra
B and
Bonelo
A
(2015). Multi-organ involvement in dengue is mediated by prominent T-cell and monocyte-macrophages responses.
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00179
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Received:
30 May 2015;
Published Online:
14 Sep 2015.
*
Correspondence:
PhD. Anilza Bonelo, Universidad del Valle, Department of Microbiology, Cali, Valle del Cauca, Colombia, anilza.bonelo@correounivalle.edu.co