Chronic hepatitis C virus infection impairs Natural Killer Cells-Dendritic Cells Crosstalk: an in-Vitro culture Study.

To examine the cross-talk between NK cells and DCs in HCV infection, we isolated monocytes and NK cells from 20 chronic HCV patients and 20 healthy controls. Monocytes were used to generate immature DCs which were pulsed with HCV peptides (core, NS3-NS4 and NS5). Four different co-cultures were carried out: E1: both DCs and NK cells were from a chronic HCV patient, E2: NK cells from a healthy control co-cultured with DCs from a chronic HCV patient, E3: NK cells from a chronic HCV patient co-cultured with DCs cells from a healthy control and E4: both DCs and NK cells were from a healthy control. Using flow cytometry, we assessed the effect of these different co-cultures on levels of maturation markers on DCs and levels of activation/inhibition markers on NK cells. Results showed that peptide pulsed HCV DCs showed a maturation defect in the form of decreased HLA-DR, decreased CD86 and increased CD83 expression especially when co-cultured with HCV NK. This was mainly due to core peptide pulsing and to a lesser extent due to NS5 pulsing whereas there was no effect with NS3-NS4 pulsing. Alternatively, HCV NK cells upregulated both activation and inhibition markers especially when co-cultured with healthy DCs. Compared to E2, E1 resulted in higher apoptosis of both NK cells and DCs with the percentage of NK apoptosis higher than that of DCs. Taken together, the data indicate that HCV infection impairs NK-DC cross-talk which may be a leading cause in viral persistence and chronicity. This article is protected by copyright. All rights reserved.