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Abstract Details
Sustained Hyperresponsiveness of Dendritic Cells is Associated with Spontaneous Resolution of Acute Hepatitis C
Pelletier S, Bédard N, Said E, Ancuta P, Bruneau J, Shoukry NH. J Virol. 2013 Apr 10. [Epub ahead of print]
Source
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital St-Luc.
Abstract
Some studies have reported that dendritic cells (DCs) may be dysfunctional in a subset of patients with chronic hepatitis C virus (HCV) infection. However, the function of DCs during acute HCV and their role in determining infectious outcome remain elusive. Here, we examined the phenotype and function of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) during acute HCV infection. Three groups of injection drug users (IDUs) at high risk of HCV infected were studied: uninfected, acute HCV infection with spontaneous resolution and acute infection with chronic evolution. We examined the frequency, maturation status and cytokine production capacity of DCs in response to the Toll like receptor (TLR)-4 and TLR-7/8 ligands lipopolysaccharide (LPS) and ssRNA, respectively. Several observations could distinguish HCV negative IDUs and acute HCV resolvers from acute patients with chronic evolution. First, we observed a decrease in the frequency of mature CD86+, PDL1+ and PDL2+ pDCs. This phenotype was associated with increased sensitivity of pDCs from resolvers and HCV negative IDUs versus chronics to ssRNA stimulation in vitro. Second, LPS-stimulated mDCs from resolvers and HCV negative IDUs produced higher levels of cytokines as compared to chronics. Third, mDCs from all acute HCV patients, irrespective of their outcomes, produced higher levels of cytokines during the early acute phase in response to ssRNA when compared to healthy controls. However, this hyperresponsiveness was sustained only in spontaneous resolvers. Altogether, our results suggest that immature pDC phenotype and sustained pDC and mDC hyperresponsiveness are associated with spontaneous resolution of acute HCV infection.