title: Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles.
abstract: Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus (DENV) and yellow fever virus (YF) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF)-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.
authors: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
authors: Mariana
authors: M
authors: Gandini
authors: Sonia Regina Nogueira Ignacio
authors: SR
authors: Reis
authors: Amanda
authors: A
authors: Torrentes-Carvalho
authors: Elzinandes Leal
authors: EL
authors: Azeredo
authors: Marcos da Silva
authors: Mda S
authors: Freire
authors: Ricardo
authors: R
authors: Galler
authors: Claire Fernandes
authors: CF
authors: Kubelka
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D003715:Dengue / Q000276:immunology* / Q000821:virology; D053059:Dengue Vaccines / Q000276:immunology; D003716:Dengue Virus / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication; D015004:Yellow Fever / Q000276:immunology* / Q000821:virology; D022341:Yellow Fever Vaccine / Q000276:immunology; D015005:Yellow fever virus / Q000276:immunology* / Q000502:physiology
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D053059:Dengue Vaccines; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D022341:Yellow Fever Vaccine