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

被引：23

作者：

Deng, Guangying ^{[1
]}

Ge, Jun ^{[1
]}

Liu, Chao ^{[1
]}

Pang, Jinke ^{[1
]}

Huang, Zuxiong ^{[1
,2
]}

Peng, Jie ^{[1
]}

Sun, Jian ^{[1
]}

Hou, Jinlin ^{[1
,3
]}

Zhang, Xiaoyong ^{[1
,3
]}

机构：

[1] Southern Med Univ, State Key Lab Organ Failure Res, Guangdong Prov Key Lab Viral Hepatitis Res, Dept Hepatol Unit & Infect Dis,Nanfang Hosp, 1838,North Guangzhou Ave, Guangzhou 510515, Guangdong, Peoples R China

[2] Fujian Med Univ, Affiliated Infect Dis Hosp, Dept Hepatol, Fuzhou, Fujian, Peoples R China

[3] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou, Zhejiang, Peoples R China

来源：

CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY | 2017年 / 41卷 / 04期

基金：

高等学校博士学科点专项科研基金; 中国国家自然科学基金;

关键词：

CHRONIC HEPATITIS-B; INNATE IMMUNE-RESPONSES; TOLL-LIKE RECEPTORS; NONPARENCHYMAL LIVER-CELLS; BLOOD MONONUCLEAR-CELLS; C VIRUS-INFECTIONS; GAMMA PRODUCTION; NATURAL-HISTORY; GENE-EXPRESSION; ACTIVATION;

D O I：

10.1016/j.clinre.2016.12.006

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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-alpha-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-alpha 2a therapy. RESULTS: TLR8 was mainly expressed in monocytes, and simulation with its ligand resulted in high levels of IFN-gamma and TNF-alpha production. Compared with healthy controls, PBMCs obtained from CHB patients displayed reduced levels of TLR8 expression and IFN-gamma, TNF-alpha 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-gamma or TNF-alpha neutralizing antibodies could block the antiviral effect. NK cells and T cells were the principal IFN-gamma-producing lymphocytes after ssRNA40 stimulation, whereas monocytes were the primary source of TNF-alpha. 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-alpha-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-alpha-2a therapy. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：386 / 398

页数：13

共 42 条

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