Back to Journals » Infection and Drug Resistance » Volume 12

Antiviral and immunomodulatory effects of polyphenols on macrophages infected with dengue virus serotypes 2 and 3 enhanced or not with antibodies

Authors Jasso-Miranda C, Herrera-Camacho I, Flores-Mendoza LK, Dominguez F, Vallejo-Ruiz V, Sanchez-Burgos GG, Pando-Robles V, Santos-Lopez G, Reyes-Leyva J

Received 2 April 2019

Accepted for publication 26 May 2019

Published 1 July 2019 Volume 2019:12 Pages 1833—1852

DOI https://doi.org/10.2147/IDR.S210890

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Melinda Thomas

Peer reviewer comments 2

Editor who approved publication: Dr Sahil Khanna


Carolina Jasso-Miranda,1,2 Irma Herrera-Camacho,2 Lilian Karem Flores-Mendoza,3 Fabiola Dominguez,1 Veronica Vallejo-Ruiz,1 Gilma Guadalupe Sanchez-Burgos,4 Victoria Pando-Robles,5 Gerardo Santos-Lopez,1 Julio Reyes-Leyva1

1Laboratory of Immunology and Virology, East Biomedical Research Center, Mexican Institute of Social Security (IMSS), CP 74360 Metepec, Puebla, México; 2Laboratory of Biochemistry and Molecular Biology, Center of Chemistry, Institute of Sciences, Meritorious Autonomous University of Puebla, CP 72570 San Manuel, Puebla, Mexico; 3Department of Chemical, Biologic and Agricultural Sciences, Science and Enginery Division, University of Sonora, CP 85880 Navojoa, Sonora, Mexico; 4Yucatan’s Medical Research Unit, Mexican Institute of Social Security (IMSS), CP 97150 Merida, Yucatan, Mexico; 5Infectious Disease Research Center, National Institute of Public Health, CP 62100 Cuernavaca, Morelos, Mexico

Background: There is a lack of specific antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-neutralizing antibodies enhance DENV infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of severe dengue.
Purpose: To identify the antiviral and immunomodulatory effects of polyphenols on dengue virus infection.
Methods: Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of tumor necrosis factor-alpha, IL-6, IL-10 and interferon-alpha were analyzed timely.
Results: DENV infection alone induced high production of IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on anti-inflammatory antecedents, the polyphenols curcumin, fisetin, resveratrol, apigenin, quercetin and rutin were tested for antiviral and immunomodulatory properties. Only quercetin and fisetin inhibited DENV-2 and DENV-3 infection in the absence or presence of enhancing antibody (>90%, p<0.001); they also inhibited TNF-α and IL-6 secretion (p<0.001).
Conclusion: Quercetin and fisetin down-regulate the production of proinflammatory cytokines induced by DENV infection enhanced by antibodies a mechanism involved in severe dengue.

Keywords: dengue, proinflammatory cytokines, TNF-α, enhancing antibody, immunopathogenesis

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]