Lu Xiaobo, Xu Qi, Bu Xianyu, Ma Xiuming, Zhang Fengbo, Deng Qiang, Zhang Yuexin, Ding Jianbing
Department of Infectious Diseases, The First affiliated Hospital of Xinjiang Medical University Urumqi 830054, Xinjiang, China.
Department of Immunology, College of Basic Medical Sciences, Xinjiang Medical University Urumqi 830011, Xinjiang, China.
Int J Clin Exp Pathol. 2014 Aug 15;7(9):6048-55. eCollection 2014.
This study is to explore the relationship between the chronic hepatitis B virus (HBV) infection and the expressions of toll-like receptor 2/4 (TLR2/4) in peripheral blood dendritic cells (DCs), to find out the immunological significance of TLR2/4 in HBV progression.
Patients had been divided into the HBV, HBV-related liver cirrhosis (HBV-LC), and HBV-related hepatocellular carcinoma (HBV-HCC) groups. Healthy individuals served as normal controls (NC). Flow cytometry was used to determine the percentage of DCs in peripheral blood, and the expression of TLR2/4 in DCs as well as the expression of HBeAg. Real-time quantitative PCR was performed to measure the content of HBV-DNA.
The percentages of DCs in peripheral blood exhibited a slightly decreasing trend, without statistical significances, along with the disease severity in HBV patients (9.40 ± 2.05%, 7.11 ± 3.82%, 6.51 ± 4.38% and 6.00 ± 4.73% for the groups of NC, HBV, HBV-LC, and HBV-HCC, respectively). The expression of TLR2 was significantly increased in the disease progression, with the TLR2 expression rates of 2.60 ± 1.70%, 2.67 ± 2.89%, 3.53 ± 3.41% and 5.11 ± 4.93 for NC, HBV, HBV-LC, HBV-HCC, respectively. Similar results were found for TLR4 (expression rates: 45.34 ± 4.46%, 53.94 ± 5.21%, 65.16 ± 5.92% and 75.54 ± 6.12%), which was positively correlated with TLR2. Furthermore, the HBeAg level was increased, while the amount of HBV-DNA exhibited a declining trend, along with the disease severity. Correlation analysis revealed that the expression of HBeAg was positively correlated with TLR2.
The elevated expressions of TLR2/4 on DC cell surfaces in peripheral blood may synergistically promote the disease progression of chronic HBV infection.
本研究旨在探讨慢性乙型肝炎病毒(HBV)感染与外周血树突状细胞(DCs)中Toll样受体2/4(TLR2/4)表达之间的关系,以明确TLR2/4在HBV病情进展中的免疫学意义。
将患者分为HBV组、HBV相关肝硬化(HBV-LC)组和HBV相关肝细胞癌(HBV-HCC)组。健康个体作为正常对照(NC)。采用流式细胞术检测外周血中DCs的百分比、DCs中TLR2/4的表达以及HBeAg的表达。采用实时定量PCR检测HBV-DNA含量。
随着HBV患者病情加重,外周血中DCs的百分比呈轻微下降趋势,但无统计学意义(NC组、HBV组、HBV-LC组和HBV-HCC组分别为9.40±2.05%、7.11±3.82%、6.51±4.38%和6.00±4.73%)。在疾病进展过程中,TLR2的表达显著增加,NC组、HBV组、HBV-LC组、HBV-HCC组的TLR2表达率分别为2.60±1.70%、2.67±2.89%、3.53±3.41%和5.11±4.93%。TLR4也有类似结果(表达率分别为45.34±4.46%、53.94±5.21%、65.16±5.92%和75.54±6.12%),且与TLR2呈正相关。此外,随着疾病严重程度增加,HBeAg水平升高,而HBV-DNA量呈下降趋势。相关性分析显示,HBeAg的表达与TLR2呈正相关。
外周血DC细胞表面TLR2/4表达升高可能协同促进慢性HBV感染的疾病进展。