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Dendritic cell maturation in HCV infection: altered regulation of MHC class I antigen processing-presenting machinery.

AbstractBACKGROUND & AIMS:
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.
AuthorsPatrizia Leone, Mariangela Di Tacchio, Simona Berardi, Teresa Santantonio, Massimo Fasano, Soldano Ferrone, Angelo Vacca, Franco Dammacco, Vito Racanelli
JournalJournal of hepatology (J Hepatol) Vol. 61 Issue 2 Pg. 242-51 (Aug 2014) ISSN: 1600-0641 [Electronic] Netherlands
PMID24732300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Cytokines
  • Histocompatibility Antigens Class I
Topics
  • Adult
  • Aged
  • Antigen Presentation
  • CD8-Positive T-Lymphocytes (immunology)
  • Cytokines (biosynthesis)
  • Dendritic Cells (physiology)
  • Female
  • Hepatitis C (immunology)
  • Histocompatibility Antigens Class I (immunology)
  • Humans
  • Male
  • Middle Aged

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