Lian Jian-Qi, Wang Xiao-Qin, Zhang Ye, Huang Chang-Xing, Bai Xue-Fan
Center of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Viral Immunol. 2009 Oct;22(5):301-8. doi: 10.1089/vim.2009.0039.
Toll-like receptors (TLRs) 2 and 4 play a key role in chronic hepatitis B virus (HBV) infection. However, the role of TLRs in the pathogenesis of HBV-related liver cirrhosis and their regulation of the innate immune response of patients with liver cirrhosis remain unknown. To assess the contribution of TLR2/4 in HBV-related liver cirrhosis, we examined the expression of circulating TLR2 and TLR4 on peripheral blood mononuclear cells (PBMCs), CD4(+)CD25(+)CD127(low/-) Treg proportions, and CD3(+)/CD4(+)/CD8(+) T-cell counts in 30 liver cirrhosis patients, 21 chronic hepatitis B (CHB) patients, and 16 normal controls (NC). Furthermore, we analyzed the relationship between TLR2/4 expression and Treg proportions and T-cell counts. We show that the expression of TLR2 and TLR4 was significantly upregulated in patients with liver cirrhosis compared to NC. TLR4 expression was significantly increased in patients with liver cirrhosis compared to patients with CHB, and for TLR2 expression there were no differences between them. TLR4 expression showed a significant positive correlation with the frequency of Tregs in liver cirrhosis patients. TLR2 expression negatively correlated with CD3(+)/CD4(+)/CD8(+) T-cell counts and HBV viral load in patients with liver cirrhosis. These findings indicate that TLR may be involved in the pathogenesis of HBV-related liver cirrhosis, and may interact with Tregs and CD3(+)/CD4(+)/CD8(+) T cells in the immune response during HBV-related liver cirrhosis.
Toll样受体（TLRs）2和4在慢性乙型肝炎病毒（HBV）感染中起关键作用。然而，TLRs在HBV相关肝硬化发病机制中的作用及其对肝硬化患者固有免疫反应的调节作用仍不清楚。为了评估TLR2/4在HBV相关肝硬化中的作用，我们检测了30例肝硬化患者、21例慢性乙型肝炎（CHB）患者和16例正常对照（NC）外周血单个核细胞（PBMCs）上循环TLR2和TLR4的表达、CD4(+)CD25(+)CD127(low/-)调节性T细胞（Treg）比例以及CD3(+)/CD4(+)/CD8(+)T细胞计数。此外，我们分析了TLR2/4表达与Treg比例和T细胞计数之间的关系。我们发现，与NC相比，肝硬化患者TLR2和TLR4的表达显著上调。与CHB患者相比，肝硬化患者TLR4表达显著增加，而TLR2表达在两者之间无差异。TLR4表达与肝硬化患者Treg频率呈显著正相关。肝硬化患者TLR2表达与CD3(+)/CD4(+)/CD8(+)T细胞计数及HBV病毒载量呈负相关。这些发现表明，TLR可能参与HBV相关肝硬化的发病机制，并可能在HBV相关肝硬化免疫反应中与Treg及CD3(+)/CD4(+)/CD8(+)T细胞相互作用。
