title: NK cells lacking FcεRIγ are associated with reduced liver damage in chronic hepatitis C virus infection.
abstract: A novel subset of human natural killer (NK) cells, which displays potent and broad antiviral responsiveness in concert with virus-specific antibodies, was recently uncovered in cytomegalovirus (CMV)+ individuals. This NK-cell subset (g-NK) was characterized by a deficiency in the expression of FcεRIγ adaptor protein and the long-lasting memory-like NK-cell phenotype, suggesting a role in chronic infections. This study investigates whether the g-NK-cell subset is associated with the magnitude of liver disease during chronic hepatitis C virus (HCV) infection. Analysis of g-NK-cell proportions and function in the PBMCs of healthy controls and chronic HCV subjects showed that chronic HCV subjects had slightly lower proportions of the g-NK-cell subset having similarly enhanced antibody-dependent cellular cytotoxicity responses compared to conventional NK cells. Notably, among CMV+ chronic HCV patients, lower levels of liver enzymes and fibrosis were found in those possessing g-NK cells. g-NK cells were predominant among the CD56(neg) NK cell population often found in chronic HCV patients, suggesting their involvement in immune response during HCV infection. For the first time, our findings indicate that the presence of the g-NK cells in CMV+ individuals is associated with amelioration of liver disease in chronic HCV infection, suggesting the beneficial roles of g-NK cells during a chronic infection.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
authors.forename: Jun S
authors.initials: JS
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
authors.forename: Alaa K
authors.initials: AK
authors.lastname: Ali
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA.
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Corsi
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Canada.|Division of Infectious Diseases, Ottawa Hospital-General Campus, Ottawa, Canada.|School of Epidemiology, Public Health and Preventative Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Cooper
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics / Q000276:immunology; D019002:CD56 Antigen / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D017455:Receptors, IgE / Q000235:genetics* / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019002:CD56 Antigen; C543372:FcepsilonRI gamma-chain, human; C522918:NCAM1 protein, human; D017455:Receptors, IgE
keywords: ADCC ⋅ Cytomegalovirus (CMV) ⋅ Hepatitis C virus (HCV) ⋅ Liver enzymes ⋅ Liver fibrosis ⋅ Natural killer (NK) cells