Abstract
The innate immunopathogenesis responsible for the susceptibility to hepatocyte injury in chronic hepatitis B surface antigen carriers is not well defined. In this study, hepatitis B virus (HBV) transgenic mice (named HBs-Tg) were oversensitive to liver injury after immunologic [polyinosinic:polycytidylic acid or concanavalin A (ConA)] or chemical (CCl4) triggering. It was then found that the nonhepatotoxic low dose of ConA for wild-type mice induced severe liver injury in HBs-Tg mice, which was dependent on the accumulated intraheptic natural killer (NK) cells. Expressions of NKG2D ligands (Rae-1 and Mult-1) in hepatocytes were markedly enhanced upon ConA stimulation in HBs-Tg mice, which greatly activated hepatic NK cells via NKG2D/Rae-1 or Mult-1 recognition. Interestingly, the presence of NK T cells was necessary for NK cell activation and worked as positive helper cell possibly by producing interferon-gamma and interleukin-4 in this process.
Conclusion:
Our findings for the first time suggested the critical role of NKG2D recognition of hepatocytes by NK cells in oversensitive liver injury during chronic HBV infection.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Carbon Tetrachloride / toxicity
-
Carrier Proteins / metabolism
-
Carrier State / immunology*
-
Chemical and Drug Induced Liver Injury / immunology*
-
Chemical and Drug Induced Liver Injury / pathology
-
Concanavalin A / toxicity
-
Disease Susceptibility
-
Hepatitis B Surface Antigens / genetics
-
Hepatitis B Surface Antigens / immunology*
-
Hepatitis B virus / genetics
-
Hepatitis B virus / immunology*
-
Histocompatibility Antigens Class I / metabolism
-
Killer Cells, Natural / immunology*
-
Ligands
-
Liver / pathology
-
Membrane Proteins
-
Mice
-
Mice, Transgenic
-
NK Cell Lectin-Like Receptor Subfamily K
-
Nuclear Matrix-Associated Proteins / metabolism
-
Nucleocytoplasmic Transport Proteins / metabolism
-
Receptors, Immunologic / metabolism*
-
Receptors, Natural Killer Cell
Substances
-
Carrier Proteins
-
Hepatitis B Surface Antigens
-
Histocompatibility Antigens Class I
-
Klrk1 protein, mouse
-
Ligands
-
Membrane Proteins
-
NK Cell Lectin-Like Receptor Subfamily K
-
Nuclear Matrix-Associated Proteins
-
Nucleocytoplasmic Transport Proteins
-
Rae1 protein, mouse
-
Receptors, Immunologic
-
Receptors, Natural Killer Cell
-
UL16 binding protein 1, mouse
-
Concanavalin A
-
Carbon Tetrachloride