Severe dendritic cell perturbation is actively involved in the pathogenesis of acute-on-chronic hepatitis B liver failure.
OBJECTIVE
Functionally impaired dendritic cells (DCs) play important roles in suppressing host immune responses and facilitating viral persistence in chronic hepatitis B virus (HBV) infection. However, little is known regarding the status of intrahepatic DCs in HBV infection.


METHODS
Based on availability, 11 recipient liver samples were obtained from acute-on-chronic hepatitis B liver failure (ACHBLF) patients who had undergone liver transplantation. The frequencies, phenotypes, and functions of intrahepatic DC subsets were analyzed.


RESULTS
Both plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs) extensively infiltrated the liver of the ACHBLF patients and expressed mature phenotypes therein. In particular, activated hepatic pDCs produced interferon (IFN)-alpha, which subsequently induced interleukin (IL)-12 and IL-10 production via toll-like receptor-9 ligation in liver-infiltrating lymphocytes cultured in vitro. However, blockade of IFN-alpha production significantly reduced the cytokine production of the LILs. Further, a significantly low frequency of peripheral pDCs and highly reduced IFN-alpha production were observed in a large cohort of the ACHBLF patients, particularly in the non-survivors. Moreover, a persistently upregulated expression of hepatic IFN-alpha-associated genes was observed in the ACHBLF patients during disease progression.


CONCLUSIONS
Activated pDCs accumulated in large numbers in the liver of the ACHBLF patients and regulated local immune responses in chronic HBV infection.
Zhang
Zheng
Z
Research Center for Biological Therapy, Beijing Institute of Infectious Diseases, Beijing 302 Hospital, Beijing 100039, China.
Zou
Zheng-Sheng
ZS
Fu
Jun-Liang
JL
Cai
Lun
L
Jin
Lei
L
Liu
Yong-Jun
YJ
Wang
Fu-Sheng
FS
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002452:Cell Count; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000473:pathology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D017114:Liver Failure, Acute / Q000473:pathology* / Q000821:virology*; D016031:Liver Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011971:Receptors, Immunologic / Q000378:metabolism
C443299:CLEC4C protein, human; D016898:Interferon-alpha; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D016753:Interleukin-10; D018664:Interleukin-12