Journal
MICROBES AND INFECTION
Volume 11, Issue 4, Pages 515-523Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2009.02.008
Keywords
HBV; pDCs; TLR9; IFN-alpha
Categories
Funding
- National Natural Science Foundation of China [30671838]
- Committee of Science and Technology of Shanghai Municipal Government [044119624]
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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 patient 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 (similar to 50%) reduced, Supported by similar to 70% reduction or 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 (similar to 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. (C) 2009 Elsevier Masson SAS. All rights reserved.
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