Expression profiles and function of Toll-like receptors 2 and 4 in peripheral blood mononuclear cells of chronic hepatitis B patients.
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.
Chen
Zhiao
Z
Research Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Cheng
Yuming
Y
Xu
Yongfen
Y
Liao
Jing
J
Zhang
Xiaonan
X
Hu
Yunwen
Y
Zhang
Qin
Q
Wang
Jiefei
J
Zhang
Zhanqing
Z
Shen
Fang
F
Yuan
Zhenghong
Z
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology* / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051194:Toll-Like Receptor 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D006514:Hepatitis B Surface Antigens; D012333:RNA, Messenger; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6