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

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

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

© 2019 Jasso-Miranda et al. 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 antiinflammatory 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.
Original languageAmerican English
Pages (from-to)1833-1852
Number of pages20
JournalInfection and Drug Resistance
DOIs
StatePublished - 1 Jan 2019

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