title: Dendritic cell maturation in HCV infection: altered regulation of MHC class I antigen processing-presenting machinery.
abstract: OBJECTIVE
  Modulation of dendritic cell (DC) function has been theorized as one of the mechanisms used by hepatitis C virus (HCV) to evade the host immune response and cause persistent infection.
  
  
  METHODS
  We used a range of cell and molecular biology techniques to study DC subsets from uninfected and HCV-infected individuals.
  
  
  RESULTS
  We found that patients with persistent HCV infection have lower numbers of circulating myeloid DC and plasmacytoid DC than healthy controls or patients who spontaneously recovered from HCV infection. Nonetheless, DC from patients with persistent HCV infection display normal phagocytic activity, typical expression of the class I and II HLA and co-stimulatory molecules, and conventional cytokine production when stimulated to mature in vitro. In contrast, they do not display the strong switch from immunoproteasome to standard proteasome subunit expression and the upregulation of the transporter-associated proteins following stimulation, which were instead observed in DC from uninfected individuals. This different modulation of components of the HLA class I antigen processing-presenting machinery results in a differential ability to present a CD8(+) T cell epitope whose generation is dependent on the LMP7 immunoproteasome subunit.
  
  
  CONCLUSIONS
  Overall, these findings establish that under conditions of persistent HCV antigenemia, HLA class I antigen processing and presentation are distinctively regulated during DC maturation.
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Leone
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Di Tacchio
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Berardi
authors.affiliation: Department of Infectious Diseases, University of Foggia, Foggia, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
authors.affiliation: Department of Infectious Diseases, University of Foggia, Foggia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fasano
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. Electronic address: vito.racanelli1@uniba.it.
authors.forename: Vito
authors.initials: V
authors.lastname: Racanelli
mesh_terms: D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006526:Hepatitis C / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D016207:Cytokines; D015395:Histocompatibility Antigens Class I
keywords: Antigen processing machinery; Dendritic cells; HCV
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