Patients with chronic hepatitis B infection display deficiency of plasmacytoid dendritic cells with reduced expression of TLR9.
Chronic hepatitis B virus (HBV) infection is a complex interaction between replicating noncytopathic virus and dysregulatory host antiviral immunity. Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immunity via secreting type I interferons. Toll-like receptor (TLR) 9 is involved in major pattern recognition receptors expressed in pDCs. The frequency of pDCs and TLR9 expression in peripheral blood mononuclear cells (PBMC) was determined, using flow cytometry. IFN-alpha production by PBMC was evaluated in vitro in the presence of cytidine phosphate guanosine (CpG) with/without pDCs. The correlation between TLR9, pDCs frequency and viral load was also evaluated. TLR9 expression in pDCs in chronic HBV patients was significantly ( approximately 50%) reduced, supported by approximately 70% reduction of TLR9 mRNA, in comparison to healthy controls, correlating with the impairment of IFN-alpha production in vitro. Furthermore, pDCs frequency in these patients was substantially reduced ( approximately 30%), inversely correlating with serum ALT levels and HBV viral load. HBsAg and HBcAg were detected by immunohistochemistry in pDCs in chronic HBV patients. We conclude that HBV infection results in reduced frequency of circulating pDCs and their functional impairment via inhibiting the expression of TLR9. These data may provide useful information in both basic research and clinical treatment of chronic HBV infection.
Xie
Qing
Q
Department of Infectious Disease, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People's Republic of China. xieqingrj@yahoo.com.cn
Shen
Huai-Cheng
HC
Jia
Ni-Na
NN
Wang
Hui
H
Lin
Lan-Yi
LY
An
Bao-Yan
BY
Gui
Hong-Lian
HL
Guo
Si-Min
SM
Cai
Wei
W
Yu
Hong
H
Guo
Qing
Q
Bao
Shisan
S
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006512:Hepatitis B Core Antigens / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis*; D019562:Viral Load; D055815:Young Adult
D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D000410:Alanine Transaminase