title: Aberrant expression and dysfunction of TLR2 and its soluble form in chronic HBV infection and its regulation by antiviral therapy.
abstract: Toll-like receptor 2 (TLR2) plays an important role in the immunopathogenesis of hepatitis B virus (HBV) infection. The relationship between TLR2 expression and clinical outcome of chronic HBV infection is not yet elucidated in details so far. Here, we employed clinical cohorts to investigate TLR2 expression and function in different phases of HBV infection and dynamic changes of TLR2 expression in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral therapy. TLR2 was mainly expressed in monocytes and its ligand stimulation resulted in TNF-α, IL-6 and IL-10 production. Serum soluble TLR2 (sTLR2) levels were negatively correlated with TLR2 mRNA in PBMCs. As compared with immunotolerant carriers and inactive carriers, CHB patients showed an elevated TLR2 expression and TNF-α, IL-6 induction in PBMC, but had a decreased level of sTLR2 in serum. However, TLR2 expression and TNF-α induction in monocytes of CHB patients remained lower than healthy controls. Furthermore, higher TLR2 expression in PBMCs and lower level of sTLR2 in serum at baseline were predictive of a complete response to 52 weeks of telbivudine (LdT) therapy. Temporal dynamic analysis showed that TLR2 expression was restored with viral suppression and ALT normalization from week 12 to 24. However, peg-IFN-α-2a therapy induced a slightly decline in TLR2 expression. In conclusion, TLR2 expression and function in monocytes were impaired by chronic HBV infection. Higher TLR2 expression in PBMC and lower level of sTLR2 in serum at baseline were associated with a complete response to LdT therapy, and dynamic TLR2 expression was differently regulated by LdT and peg-IFN-α-2a therapy.
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Hepatology, Affiliated Infectious Disease Hospital of Fujian Medical University, Fuzhou, China. Electronic address: huangzuxiong215@hotmail.com.
authors.forename: Zuxiong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: gejunnf@foxmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: pangjinke2006@gmail.com.
authors.forename: Jinke
authors.initials: J
authors.lastname: Pang
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: liuhongyan205628@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: chjj@smu.edu.cn.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hepatology, Guangzhou No. 8 People's Hospital, Guangzhou Medical University, Guangzhou, China. Electronic address: polinlbl@163.com.
authors.forename: Baolin
authors.initials: B
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: xhuang2000@foxmail.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China. Electronic address: zdaming@gmail.com.
authors.forename: Daming
authors.initials: D
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: sunjian@fimmu.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Institute of Virology, University Hospital of Essen, Essen, Germany. Electronic address: mengji.lu@uni-due.de.
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China. Electronic address: xiaoyong.zhang@msn.com.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China. Electronic address: jlhousmu@163.com.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D015850:Interleukin-6; D011994:Recombinant Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D000077712:Telbivudine; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a; D013936:Thymidine
keywords: Chronic hepatitis B; Hepatitis B virus; Pegylated interferon; Telbivudine; Toll-like receptor 2