Gene expression analysis during acute hepatitis C virus infection associates dendritic cell activation with viral clearance

Background and Aims: Viral clearance during acute hepatitis C virus (HCV) infection is associated with the induction of potent antiviral T-cell responses. Since dendritic cells (DC) are essential in the activation of primary T-cell responses our goal was to analyze gene expression in DC from patients during acute HCV infection. Methods: By using microarrays, gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from those who become chronically infected (ANR), as well as in HCV chronically infected patients (CHR) and healthy seronegative individuals (CTRL). Results: For pDC, a high number of upregulated genes related to different functions and processes was found in AR patients, irrespective of DC stimulation. However, for mDC, most evident differences were detected after DC stimulation, again corresponding to upregulated genes in AR patients. Differences between AR and ANR were also observed when comparing their DC with those from CHR patients and CTRL individuals. Most differences corresponded to metabolism-associated genes, with upregulation in AR patients of genes belonging to pathways associated with DC activation and cytokine responses. Conclusion: Our results show that upregulation of relevant genes in DC during acute HCV infection may determine viral clearance, suggesting that dysfunctional DC may be responsible for the lack of efficient T-cell responses which lead to chronic HCV infection. Gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from those who become chronically infected (ANR), as well as in HCV chronically infected patients (CHR) and healthy seronegative individuals (CTRL)