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

Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
Memórias do Instituto Oswaldo Cruz (Impact Factor: 1.59). 08/2011; 106(5):594-605. DOI: 10.1590/S0074-02762011000500012
Source: PubMed


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.

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Available from: Marcos da Silva Freire, Jul 19, 2014
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    • "The infected cells exhibited increased expression of inflammatory genes and the IP-10 protein and elevated intracellular calcium36. Dengue virus infection has also been associated with increased production of inflammatory cytokines which may cause muscle injury11,12. "
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    ABSTRACT: Renal histology results are very scarce in dengue-associated rhabdomyolysis patients developing acute kidney injury (AKI). We report a case of dengue fever-induced AKI associated to rhabdomyolysis with a renal biopsy showing acute tubular necrosis (ATN) and renal deposition of myoglobin. A 28-year-old patient who presented dengue fever (DF) complicated by severe AKI and rhabdomyolysis is described. The patient required hemodialysis for three weeks. A renal biopsy revealed ATN with positive staining for myoglobin in the renal tubuli. The patient was discharged with recovered renal function. In conclusion, this case report described a biopsy proven ATN associated to DF-induced rhabdomyolysis, in which renal deposition of myoglobin was demonstrated. We suggest that serum creatine phosphokinase should be monitored in DF patients to allow for an early diagnosis of rhabdomyolysis and the institution of renal protective measures.
    Revista do Instituto de Medicina Tropical de São Paulo 04/2014; 56(1):85-88. DOI:10.1590/S0036-46652014000100014 · 1.01 Impact Factor
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    • "It is noteworthy that three of four TLRs involved in recognizing YF 17D virus have as major ligands nucleic acids, pointing to the dependence of replication for YF 17D virus recognition by DCs. In response to the TLRs engagement by virus products, DCs release several proinflammatory cytokines and chemokines, among then, IL-12 and IFN-α [4,37]. It is well known that genes associated with type I IFNs are early molecular signatures of successful YF 17D vaccination, with several interferon-stimulated genes (ISGs), such as interferon related factor 7 (IRF-7), being correlated with the onset of protective immunity [6]. "
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    ABSTRACT: Yellow Fever vaccine is one of the most efficacious human vaccines ever made. The vaccine (YF 17D) virus induces polyvalent immune responses, with a mixed TH1/TH2 CD4(+) cell profile, which results in robust T CD8(+) responses and high titers of neutralizing antibody. In recent years, it has been suggested that early events after yellow fever vaccination are crucial to the development of adequate acquired immunity. We have previously shown that primary immunization of humans and monkeys with YF 17D virus vaccine resulted in the early synthesis of IFN-γ. Herein we have demonstrated, for the first time that early IFN-γ production after yellow fever vaccination is a feature also of murine infection and is much more pronounced in the C57BL/6 strain compared to the BALB/c strain. Likewise, in C57BL/6 strain, we have observed the highest CD8(+) T cells responses as well as higher titers of neutralizing antibodies and total anti-YF IgG. Regardless of this intense IFN-γ response in mice, it was not possible to see higher titers of IgG2a in relation to IgG1 in both mice lineages. However, IgG2a titers were positively correlated to neutralizing antibodies levels, pointing to an important role of IFN-γ in eliciting high quality responses against YF 17D, therefore influencing the immunogenicity of this vaccine.
    PLoS ONE 12/2013; 8(12):e81953. DOI:10.1371/journal.pone.0081953 · 3.23 Impact Factor
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    • "We hypothesised that the clinical benefit observed in dengue patients treated with chloroquine could be due to the drug's anti-inflammatory effects, particularly because chloroquine is a tumour necrosis factor (TNF)-α inhibitor and some of the clinical manifestations in dengue patients are due to high levels of serum TNF-α (Hober et al. 1993, Pinto et al. 1999, Gandini et al. 2011). Another possible effect of chloroquine in dengue patients could be related to its antiviral action, lowering the viral load and thus the degree of immune system activation. "
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