Interferon Alpha Treatment Stimulates Interferon Gamma Expression in Type I NKT Cells and Enhances Their Antiviral Effect Against Hepatitis C Virus
Overview
Authors
Affiliations
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-α 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-α 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-α, serum concentrations of IFN-γ increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-γ. Mice in which IFN-γ 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-α. These results show that IFN-α stimulates IFN-γ 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.
Cui G, Abe S, Kato R, Ikuta K Front Immunol. 2024; 15:1349184.
PMID: 38440725 PMC: 10910067. DOI: 10.3389/fimmu.2024.1349184.
Natural Killer T Cell Diversity and Immunotherapy.
Tognarelli E, Gutierrez-Vera C, Palacios P, Pasten-Ferrada I, Aguirre-Munoz F, Cornejo D Cancers (Basel). 2023; 15(24).
PMID: 38136283 PMC: 10742272. DOI: 10.3390/cancers15245737.
Kenzhetaeva T, Lukyanenko N, Kaliakpar D, Dolinnaya V, Tkachenko O Clin Exp Immunol. 2023; 213(3):310-316.
PMID: 37094821 PMC: 10570989. DOI: 10.1093/cei/uxad047.
Innate-like T lymphocytes in chronic liver disease.
Papanastasatou M, Verykokakis M Front Immunol. 2023; 14:1114605.
PMID: 37006304 PMC: 10050337. DOI: 10.3389/fimmu.2023.1114605.
New insights into iNKT cells and their roles in liver diseases.
Gu X, Chu Q, Ma X, Wang J, Chen C, Guan J Front Immunol. 2022; 13:1035950.
PMID: 36389715 PMC: 9643775. DOI: 10.3389/fimmu.2022.1035950.