HBeAg对健康人单核细胞来源树突状细胞表面TLR2和PD-L1表达水平的影响

The Influence of Hepatitis Be Antigen on the Expression of Toll-like Receptor 2 and PD-L1 on Monocyte-derived Dendritic Cells

目的:观察乙型肝炎e抗原(HBeAg)对健康人单核细胞来源的树突状细胞(Dendritic cells,DCs)表面Toll样受体2(TLR 2)和程序性死亡配体-1(PD-L1)表达的影响,进一步探讨乙肝病毒感染慢性化过程中HBeAg的作用机制。方法:利用Ficoll分离法分离健康人外周血单个核细胞,经重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)、重组人白细胞介素4(rhIL-4)诱导培养树突状细胞,将第7天的细胞分成三组,分别为HBeAg刺激组、OVA无关蛋白对照组和未刺激组,经流式细胞仪检测CD11c+细胞表面TLR 2以及PD-L1的表达水平。结果:健康人单核细胞来源的树突状细胞经过HBeAg刺激9 h后,CD11c+细胞表面TLR 2的表达水平较未刺激组以及OVA无关蛋白对照组明显下降(P<0.01),同时可见CD11c+细胞表面PD-L1表达水平显著增加(P<0.01)。结论:HBeAg可以下调DCs表面TLR 2受体的表达,并上调其表面负性调节因子PD-L1的表达。HBV可通过HBeAg作用于抗原递呈细胞相关表面受体,从而影响了其正常功能,并最终影响免疫系统对病毒的清除作用,导致乙肝病毒感染的慢性化。

Objective： To investigate the expression of Toll-like receptor 2（TLR 2） and Programmed death-ligand-1（PD-L1） on m- onoeyte-derived dendritic cells by hepatitis B e antigen, to further explore the mechanism of HBeAg in chronic hepatitis B virus infection process. Methods： I0 healthy volunteers were included in this study .We incubated and induced DC subsets differentiated from peripheral blood mononuelear cells （PBMCs） by rhGM-CSF and rhIL-4. All the DCs were classified into three groups randomly, the HBeAg interv- ention group,the OVA group and the control group. Detect the expression of TLR 2 and PD-L1 on CD11c^＋ cells of all groups by the flow cytometry. Results： After the HBeAg intervention, we observe that on the 9 hour time point, the expression of TLR 2 significantly decreased and PD-L 1 expression significantly increased on CD 11 c^＋ cells than the OVA group and the control group （P〈0.01 ）. Conclusions： HBeAg may suppress the innate immune response by decreasing the expression of TLR 2 and increasing the expression of PD-L1 on dendritic cells, which may keep HBV well-shielded from immune attack.