title: Defective natural killer cell anti-viral capacity in paediatric HBV infection.
abstract: Natural killer (NK) cells exhibit dysregulated effector function in adult chronic hepatitis B virus (HBV) infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell interferon (IFN)-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells suggests a role of impaired NK-dendritic cell (DC) cellular interactions as a potential mechanism leading to reduced IFN-γ production. The finding that NK cells are already defective in paediatric CHB, albeit less extensively than in adult CHB, has potential implications for the timing of anti-viral therapy aiming to restore immune control.
authors.affiliation: Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: I L
authors.initials: IL
authors.lastname: Heiberg
authors.forename: L J
authors.initials: LJ
authors.lastname: Pallett
authors.forename: T N
authors.initials: TN
authors.lastname: Winther
authors.forename: B
authors.initials: B
authors.lastname: Høgh
authors.forename: M K
authors.initials: MK
authors.lastname: Maini
authors.forename: D
authors.initials: D
authors.lastname: Peppa
mesh_terms: D000293:Adolescent; D000956:Antigens, Viral / Q000276:immunology; D002450:Cell Communication; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D015536:Down-Regulation; D005260:Female; D006509:Hepatitis B / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008297:Male; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000235:genetics / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D007371:Interferon-gamma
keywords: IFN-γ; NK cells; NKp30; anti-viral function; paediatric HBV infection