NKG2D modulates aggravation of liver inflammation by activating NK cells in HBV infection

Hepatitis B virus (HBV) infection is thought to be an immune-mediated liver disease. The mechanisms underlying natural killer (NK) cell group 2D receptor (NKG2D) that activates NK cells and participates in anti-HBV immunity and immunopathology has not been thoroughly elucidated. Peripheral NKG2D(+) and IFN-gamma(+) NK cells frequencies and intrahepatic NKG2D and IFN-gamma mRNA and protein expressions were determined in HBV-infected patients. Levels of NKG2D and IFN-gamma mRNA and protein in NK cells, co-cultured with HBV-replicating HepG2 cells with or without NKG2D blockade, were analyzed. Serum and supernatant IFN-gamma, TNF-alpha, perforin and granzyme B were measured. In results, peripheral NKG2D(+) and IFN-gamma(+) NK cells frequencies, intrahepatic NKG2D and IFN-. mRNA and protein levels, and serum IFN-gamma, TNF-alpha, perforin and granzyme B levels were all highest in HBV-related acute-on-chronic liver failure group, followed by chronic hepatitis B and chronic HBV carrier groups. In vitro, NKG2D and IFN-gamma mRNA and protein levels were higher in NK cells with IFN-a stimulation than without stimulation. Supernatant IFN-gamma, TNF-alpha, perforin and granzyme B levels were increased under co-culture or IFN-alpha stimulating conditions, but were partially blocked by NKG2DmAb. In conclusion, NKG2D regulates immune inflammation and anti-viral response partly through activation of NK cells during HBV infection.