title: Patients with chronic hepatitis B infection display deficiency of plasmacytoid dendritic cells with reduced expression of TLR9.
abstract: 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.
authors.affiliation: Department of Infectious Disease, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People's Republic of China. xieqingrj@yahoo.com.cn
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Huai-Cheng
authors.initials: HC
authors.lastname: Shen
authors.forename: Ni-Na
authors.initials: NN
authors.lastname: Jia
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Lan-Yi
authors.initials: LY
authors.lastname: Lin
authors.forename: Bao-Yan
authors.initials: BY
authors.lastname: An
authors.forename: Hong-Lian
authors.initials: HL
authors.lastname: Gui
authors.forename: Si-Min
authors.initials: SM
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
mesh_terms: 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
chemical_list: 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