Hepatitis C virus-infected cells downregulate NKp30 and inhibit ex vivo NK cell functions.
J Immunol
; 191(6): 3308-18, 2013 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-23960237
ABSTRACT
Hepatitis C virus (HCV) successfully evades the immune system and establishes chronic infection in â¼80% of cases. Immune evasion may involve modulating NK cell functions. Therefore, we developed a short-term assay to assess immediate effects of HCV-infected cells on ex vivo NK cytotoxicity and cytokine production. Natural cytotoxicity, Ab-dependent cell-mediated cytotoxicity, IFN-γ production, and TNF-α production were all significantly inhibited by short-term direct exposure to HCV-infected hepatoma-derived Huh-7.5 cells. Inhibition required cell-to-cell contact and increased together with multiplicity of infection and HCV protein levels. Blocking potential interaction between HCV E2 and NK CD81 did not abrogate NK cell inhibition mediated by HCV-infected cells. We observed no change in expression levels of NKG2D, NKG2A, NKp46, or CD16 on NK cells exposed to HCV-infected Huh-7.5 cells for 5 h or of human histocompatibility-linked leukocyte Ag E on HCV-infected compared with uninfected Huh-7.5 cells. Inhibition of ex vivo NK functions did correspond with reduced surface expression of the natural cytotoxicity receptor NKp30, and downregulation of NKp30 was functionally reflected in reduced anti-NKp30 redirected lysis of P815 cells. Infection of Huh-7.5 cells with HCV JFH1(T) increased surface binding of an NKp30-IgG1 Fcγ fusion protein, suggesting upregulation of an antagonistic NKp30 ligand on HCV-infected cells. Our assay demonstrates rapid inhibition of critical NK cell functions by HCV-infected cells. Similar localized effects in vivo may contribute to establishment of chronic HCV infection and associated phenotypic and functional changes in the NK population.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Hepatite C
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Hepacivirus
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Receptor 3 Desencadeador da Citotoxicidade Natural
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article