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Impaired expression and function of TLR8 in chronic HBV infection and its association with treatment responses during peg-IFN-α-2a antiviral therapy

Summary Background and aim Toll-like receptor 8 (TLR8) plays an important role in controlling chronic viral infections. However, the role of TLR8 in chronic hepatitis B virus (HBV) infection is poorly understood. In this study, we aimed to investigate the expression and function of TLR8 in periphera...

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Published in:Clinics and research in hepatology and gastroenterology 2017-09, Vol.41 (4), p.386-398
Main Authors: Deng, Guangying, Ge, Jun, Liu, Chao, Pang, Jinke, Huang, Zuxiong, Peng, Jie, Sun, Jian, Hou, Jinlin, Zhang, Xiaoyong
Format: Article
Language:English
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Summary:Summary Background and aim Toll-like receptor 8 (TLR8) plays an important role in controlling chronic viral infections. However, the role of TLR8 in chronic hepatitis B virus (HBV) infection is poorly understood. In this study, we aimed to investigate the expression and function of TLR8 in peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B (CHB) patients and its alteration during peg-IFN-α-2a therapy. Methods We evaluated TLR8 expression and antiviral function in vitro by real-time RT-PCR and flow cytometry analysis using fresh PBMCs obtained from CHB patients compared to healthy controls. We also employed clinical cohorts to investigate TLR8 expression in response to peg-IFN-α-2a therapy. Results TLR8 was mainly expressed in monocytes, and simulation with its ligand resulted in high levels of IFN-γ and TNF-α production. Compared with healthy controls, PBMCs obtained from CHB patients displayed reduced levels of TLR8 expression and IFN-γ, TNF-α and IL-12 induction. The exposure of HepG2.2.15 cells to conditioned medium from PBMCs stimulated by ssRNA40 strongly reduced the levels of HBV DNA, HBsAg and HBeAg, whereas the addition of IFN-γ or TNF-α neutralizing antibodies could block the antiviral effect. NK cells and T cells were the principal IFN-γ-producing lymphocytes after ssRNA40 stimulation, whereas monocytes were the primary source of TNF-α. Analysis of the temporal dynamics showed that patients who achieved a complete response sustained a significant higher level of TLR8 mRNA than those who did not achieve a complete response beginning at week 12 of peg-IFN-α-2a therapy. Conclusions TLR8 expression and function in PBMCs were impaired by chronic HBV infection. Higher TLR8 expression after treatment week 12 could potentially predict complete response to peg-IFN-α-2a therapy.
ISSN:2210-7401
2210-741X
DOI:10.1016/j.clinre.2016.12.006