| First Author | Miyaki E | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 3 | Pages | e0172412 |
| PubMed ID | 28253324 | Mgi Jnum | J:245649 |
| Mgi Id | MGI:5916152 | Doi | 10.1371/journal.pone.0172412 |
| Citation | Miyaki E, et al. (2017) Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus. PLoS One 12(3):e0172412 |
| abstractText | Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-alpha using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). IFN-alpha treatment following human PBMC transplantation resulted in a significant reduction in serum HCV RNA titers and a higher human CD45-positive mononuclear cell chimerism compared to mice without human PBMC transplantation. In mice with human PBMCs treated with IFN-alpha, serum concentrations of IFN-gamma increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-gamma. Mice in which IFN-gamma signaling was blocked using antibody or in which transplanted PBMCs were depleted for type I NKT cells showed similar levels of anti-HCV effect compared with mice treated only with IFN-alpha. These results show that IFN-alpha stimulates IFN-gamma expression in type 1 NKT cells and enhances the inhibition of HCV replication. We propose that type 1 NKT cells might represent a new therapeutic target for chronic hepatitis C patients. |
