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 monocytederived 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.Key words: cytokines -dendritic cells -dengue virus -yellow fever vaccine -flavivirus dendritic cell activation by flavivirus • Mariana Gandini et al.

Biopsy Proven Acute Tubular Necrosis Due to Rhabdomyolysis in a Dengue Fever Patient: A Case Report and Review of Literature

“…The infected cells exhibited increased expression of inflammatory genes and the IP-10 protein and elevated intracellular calcium 36 . Dengue virus infection has also been associated with increased production of inflammatory cytokines which may cause muscle injury 11,12 .…”

Chloroquine use improves dengue-related symptoms

“…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.…”

T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models

“…Depending on the pathogen, type-I interferon can significantly influence the activation and proliferation of T cells [73,74]. Type-I interferon is produced by human and rhesus macaque cells infected with 17D in vitro [41,42,75,76,77,78]; however, a role for type-I interferon in YFV-specific adaptive immune responses in vivo has not been defined. Despite these concerns, 17D-specific T cells induced in IFNAR −/− mice appear to be normal, and their phenotypes align well with those seen in human studies.…”