Liver-specific HBsAg transgenic mice are over-sensitive to Poly(I:C)-induced liver injury in NK cell- and IFN-gamma-dependent manner.
OBJECTIVE
The role of natural killer (NK) cells in the development of hepatitis B virus (HBV)-associated liver injury remains obscure. In this study, we elucidated the role of NK cells in liver injury of HBsAg transgenic mice (HBs-B6), a mimic of human healthy chronic HBsAg carriers, triggered by polyinosinic:polycytidylic acid [Poly(I:C)].


METHODS
HBs-B6 or wild B6 mice were intraperitoneally injected with Poly(I:C) at different doses. Liver injury was evaluated by serum transaminase activity and histopathologic changes.


RESULTS
HBs-B6 mice were over-sensitive to Poly(I:C)-induced liver injury, which was absolutely dependent on the presence of NK cells and IFN-gamma produced by intrahepatic NK cells. Much stronger IFN-gamma receptor expression was observed on hepatocytes of HBs-B6 mice, which was significantly enhanced by Poly(I:C) injection. Treatment with IFN-gammain vitro triggered much higher activation of downstream signals (pSTAT1-IRF-1) in hepatocytes of HBs-B6 mice. Depletion of Kupffer cells and neutralization of endogenous IL-12 did not affect Poly(I:C)-induced over-sensitive liver injury in HBs-B6 mice.


CONCLUSIONS
NK cells played a critical role in an IFN-gamma dependent, Kupffer cell- and IL-12-independent manner in over-sensitive liver injury triggered by Poly(I:C) in murine chronic HBsAg carriers.
Chen
Yongyan
Y
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei City, Anhui 230027, PR China.
Sun
Rui
R
Jiang
Wei
W
Wei
Haiming
H
Tian
Zhigang
Z
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004198:Disease Susceptibility; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000502:physiology; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology*; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011070:Poly I-C / Q000494:pharmacology; D017471:Receptors, Interferon / Q000378:metabolism; D000096743:Interferon gamma Receptor
D006514:Hepatitis B Surface Antigens; D007371:Interferon-gamma; D018664:Interleukin-12; D011070:Poly I-C; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor