Background and aims HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells. Methods Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting. Culture and coculture of monocytes and NK cells were used to determine NK cell activation, using intracellular cytokines staining. Results In chronic HBV infection, monocytes express higher levels of PD-L1, HLA-E, interleukin (IL)-10 and TGF-β, and NK cells express higher levels of PD-1, CD94 and IL-10, compared with healthy individuals. HBV employs hepatitis B surface antigen (HBsAg) to induce suppressive monocytes with HLA-E, PD-L1, IL-10 and TGF-β expression via the MyD88/NFκB signalling pathway. HBV-treated monocytes induce NK cells to produce IL-10, via PD-L1 and HLA-E signals. Such NK cells inhibit autologous T cell activation. Conclusions Our findings reveal an immunosuppressive cascade, in which HBV generates suppressive monocytes, which initiate regulatory NK cells differentiation resulting in T cell inhibition.

中文翻译：

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慢性 HBV 感染中免疫抑制单核细胞和功能失调的 T 细胞之间介导的调节性 NK 细胞

背景和目的 乙型肝炎病毒感染是世界范围内的一个主要健康问题，但乙型肝炎病毒引起慢性持续性感染的免疫机制仍然只有部分了解。最近，在单核细胞和自然杀伤（NK）细胞中发现了具有抑制特征的细胞亚群。在这里，我们检查 HBV 对单核细胞和 NK 细胞的影响。方法纯化来自慢性 HBV 感染患者和健康对照的单核细胞和 NK 细胞，并通过流式细胞术、实时定量 (qRT)-PCR、ELISA 和蛋白质印迹法对表型、基因表达和细胞因子分泌进行表征。单核细胞和 NK 细胞的培养和共培养用于使用细胞内细胞因子染色来确定 NK 细胞活化。结果慢性HBV感染者与健康人相比，单核细胞表达更高水平的PD-L1、HLA-E、白细胞介素(IL)-10和TGF-β，NK细胞表达更高水平的PD-1、CD94和IL-10。个人。HBV 利用乙型肝炎表面抗原 (HBsAg) 通过 MyD88/NFκB 信号通路诱导抑制性单核细胞表达 HLA-E、PD-L1、IL-10 和 TGF-β。HBV 处理的单核细胞通过 PD-L1 和 HLA-E 信号诱导 NK 细胞产生 IL-10。此类 NK 细胞抑制自体 T 细胞活化。结论 我们的研究结果揭示了免疫抑制级联反应，其中 HBV 产生抑制性单核细胞，启动调节性 NK 细胞分化，导致 T 细胞抑制。