title: Gene expression analysis during acute hepatitis C virus infection associates dendritic cell activation with viral clearance.
abstract: 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, gene expression was analyzed in DC from patients during acute HCV infection. 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 patients who become chronically infected (ANR), as well as in healthy individuals (CTRL) and chronically-infected patients (CHR). For pDC, a high number of upregulated genes 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. Divergent behavior of ANR was also observed when analyzing DC from CTRL and CHR, with ANR patients clustering again apart from these groups. These differences corresponded to metabolism-associated genes and genes belonging to pathways relevant for DC activation and cytokine responses. Thus, 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.
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Aintzane
authors.initials: A
authors.lastname: Zabaleta
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA, Insituto de Investigación Sanitaria de Navarra, Pamplona, Spain.
authors.forename: Jose-Ignacio
authors.initials: JI
authors.lastname: Riezu-Boj
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA, Insituto de Investigación Sanitaria de Navarra, Pamplona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Larrea
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA, Insituto de Investigación Sanitaria de Navarra, Pamplona, Spain.|Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Lorea
authors.initials: L
authors.lastname: Villanueva
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA, Insituto de Investigación Sanitaria de Navarra, Pamplona, Spain.|Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Lasarte
authors.affiliation: IdiSNA, Insituto de Investigación Sanitaria de Navarra, Pamplona, Spain.|Bioinformatics Unit, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Guruceaga
authors.affiliation: Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fisicaro
authors.affiliation: Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.
authors.forename: Sayeh
authors.initials: S
authors.lastname: Ezzikouri
authors.affiliation: Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
authors.affiliation: Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.affiliation: Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Benjelloun
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA, Insituto de Investigación Sanitaria de Navarra, Pamplona, Spain.|Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA, Insituto de Investigación Sanitaria de Navarra, Pamplona, Spain.|Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Sarobe
mesh_terms: D000293:Adolescent; D000328:Adult; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged
keywords: activation; metabolism; myeloid DC; plasmacytoid DC; viral clearance