Hepatitis C Virus Core Protein Enhances Natural Killer Cell Depletion of Plasmacytoid Dendritic Cells

Abstract

Investigation of the bi-directional relationship between natural killer (NK) cells and plasmacytoid dendritic cells (pDCs) is critical in understanding antiviral immunity. In the present study, we determined whether the tumor necrosis factor apoptosis-inducing ligand (TRAIL) pathway was responsible for increased apoptosis of pDCs in hepatitis C virus (HCV) infection. We stimulated peripheral blood mononuclear cells (PBMCs) with recombinant HCV core protein within 12 hours to measure the relative expression of tumor necrosis factor apoptosis-inducing receptor 1 (TRAIL-R1) and TRAIL-R2 in pDCs using flow cytometry and image cytometry. We also measured the relative expression of TRAIL in NK cells after stimulation with recombinant HCV core protein using flow cytometry and image cytometry. Using flow cytometry, our results show that within 12 hours of stimulation, HCV core protein increases TRAIL-R1 on pDCs by 0.01%, CD56 expression by 0.66%, and TRAIL expression by 0.66%, in NK cells as compared to unstimulated PBMCs. ELISA and fluorescence spectroscopy results showed that HCV core protein decreases Bcl-2 expression in PBMCs and in pDCs by 36% and 3%, respectively. Our results suggest that HCV core protein increases NK cell deletion of pDCs, independent of the Bcl-2 pathway, contributing to HCV viral escape from immune responses, which may result in chronic HCV infection.

Keywords

• hepatitis
• innate immunity
• host response
• apoptosis
• viral pathogenesis