Defective natural killer cell anti-viral capacity in paediatric HBV infection

Clin Exp Immunol. 2015 Mar;179(3):466-76. doi: 10.1111/cei.12470.

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.

Keywords: IFN-γ; NK cells; NKp30; anti-viral function; paediatric HBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, Viral / immunology
  • Cell Communication
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cross-Sectional Studies
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • Down-Regulation
  • Female
  • Hepatitis B / immunology*
  • Hepatitis B virus / immunology*
  • Humans
  • Interferon-gamma / metabolism*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / virology
  • Male
  • Natural Cytotoxicity Triggering Receptor 3 / genetics
  • Natural Cytotoxicity Triggering Receptor 3 / metabolism

Substances

  • Antigens, Viral
  • NCR3 protein, human
  • Natural Cytotoxicity Triggering Receptor 3
  • Interferon-gamma