TY - JOUR
T1 - Expression profiles and function of Toll-like receptors 2 and 4 in peripheral blood mononuclear cells of chronic hepatitis B patients
AU - Chen, Zhiao
AU - Cheng, Yuming
AU - Xu, Yongfen
AU - Liao, Jing
AU - Zhang, Xiaonan
AU - Hu, Yunwen
AU - Zhang, Qin
AU - Wang, Jiefei
AU - Zhang, Zhanqing
AU - Shen, Fang
AU - Yuan, Zhenghong
PY - 2008/9
Y1 - 2008/9
N2 - Toll-like receptors (TLRs) play a central role in sensing and initiating innate antiviral response. In this study, we first investigated the expression of TLR1-10 mRNA transcripts in peripheral blood mononuclear cells (PBMCs) from chronic HBV-infected (CHB) patients and healthy donors by quantitative real-time PCR. The expression of TLR1, TLR2, TLR4 and TLR6 transcripts was significantly lower in PBMCs from CHB patients, and the down-regulation of TLR2 was related to HBV genotype C. Flow cytometric analysis showed that the expression of TLR2 on PBMCs was significantly decreased in CHB patients. Furthermore, impaired cytokine production was observed in PBMCs from CHB patients after challenged with TLR2 and TLR4 ligands and was correlated with the levels of plasma hepatitis B virus surface antigen (HBsAg). In conclusion, our study reveals a possible interaction between HBsAg, TLR signaling and the innate immune response, which may partially explain the mechanism of HBV infection induced immuno-tolerance.
AB - Toll-like receptors (TLRs) play a central role in sensing and initiating innate antiviral response. In this study, we first investigated the expression of TLR1-10 mRNA transcripts in peripheral blood mononuclear cells (PBMCs) from chronic HBV-infected (CHB) patients and healthy donors by quantitative real-time PCR. The expression of TLR1, TLR2, TLR4 and TLR6 transcripts was significantly lower in PBMCs from CHB patients, and the down-regulation of TLR2 was related to HBV genotype C. Flow cytometric analysis showed that the expression of TLR2 on PBMCs was significantly decreased in CHB patients. Furthermore, impaired cytokine production was observed in PBMCs from CHB patients after challenged with TLR2 and TLR4 ligands and was correlated with the levels of plasma hepatitis B virus surface antigen (HBsAg). In conclusion, our study reveals a possible interaction between HBsAg, TLR signaling and the innate immune response, which may partially explain the mechanism of HBV infection induced immuno-tolerance.
KW - Adult
KW - Cells, Cultured
KW - Cytokines/analysis
KW - Female
KW - Hepatitis B Surface Antigens/immunology
KW - Hepatitis B virus/immunology
KW - Hepatitis B, Chronic/immunology
KW - Humans
KW - Leukocytes, Mononuclear/immunology
KW - Male
KW - Middle Aged
KW - RNA, Messenger/genetics
KW - Signal Transduction
KW - Toll-Like Receptor 1/genetics
KW - Toll-Like Receptor 2/genetics
KW - Toll-Like Receptor 4/genetics
KW - Toll-Like Receptor 6/genetics
U2 - 10.1016/j.clim.2008.04.006
DO - 10.1016/j.clim.2008.04.006
M3 - Article
C2 - 18565796
SN - 1521-6616
VL - 128
SP - 400
EP - 408
JO - Clinical Immunology and Immunopathology
JF - Clinical Immunology and Immunopathology
IS - 3
ER -