Dendritic cell maturation in HCV infection: altered regulation of MHC class I antigen processing-presenting machinery.
J Hepatol
; 61(2): 242-51, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24732300
ABSTRACT
BACKGROUND & 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Antígenos de Histocompatibilidade Classe I
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Hepatite C
/
Apresentação de Antígeno
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Itália