Chen Zhiao, Cheng Yuming, Xu Yongfen, Liao Jing, Zhang Xiaonan, Hu Yunwen, Zhang Qin, Wang Jiefei, Zhang Zhanqing, Shen Fang, Yuan Zhenghong
Research Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Clin Immunol. 2008 Sep;128(3):400-8. doi: 10.1016/j.clim.2008.04.006. Epub 2008 Jun 20.
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.
Toll样受体(TLRs)在感知和启动先天性抗病毒反应中起核心作用。在本研究中,我们首先通过定量实时PCR研究了慢性乙型肝炎病毒(HBV)感染患者(CHB)和健康供体外周血单个核细胞(PBMCs)中TLR1-10 mRNA转录本的表达。CHB患者PBMCs中TLR1、TLR2、TLR4和TLR6转录本的表达显著降低,TLR2的下调与HBV C基因型有关。流式细胞术分析显示,CHB患者PBMCs上TLR2的表达显著降低。此外,用TLR2和TLR4配体刺激后,CHB患者PBMCs中观察到细胞因子产生受损,且与血浆乙型肝炎病毒表面抗原(HBsAg)水平相关。总之,我们的研究揭示了HBsAg、TLR信号传导与先天性免疫反应之间可能存在的相互作用,这可能部分解释了HBV感染诱导免疫耐受的机制。