Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China.
Institute of Liver Diseases, The First Hospital, Jilin University, Changchun, China.
Gut. 2018 Nov;67(11):2035-2044. doi: 10.1136/gutjnl-2017-314098. Epub 2017 Sep 12.
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.
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.
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.
Our findings reveal an immunosuppressive cascade, in which HBV generates suppressive monocytes, which initiate regulatory NK cells differentiation resulting in T cell inhibition.
HBV 感染是全球范围内的一个主要健康问题，但 HBV 导致慢性持续性感染的免疫机制仍知之甚少。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。在此，我们研究了 HBV 对单核细胞和 NK 细胞的影响。
从慢性 HBV 感染患者和健康对照者中纯化单核细胞和 NK 细胞，并通过流式细胞术、实时定量 (qRT)-PCR、ELISA 和 Western blot 分析其表型、基因表达和细胞因子分泌。通过细胞内细胞因子染色来确定单核细胞和 NK 细胞的共培养和共培养，以确定 NK 细胞的激活。
在慢性 HBV 感染中，与健康个体相比，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，而 NK 细胞表达更高水平的 PD-1、CD94 和 IL-10。HBV 通过 MyD88/NFκB 信号通路利用乙型肝炎表面抗原 (HBsAg) 诱导表达 HLA-E、PD-L1、IL-10 和 TGF-β 的抑制性单核细胞。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。这种 NK 细胞抑制自身 T 细胞激活。
我们的研究结果揭示了一个免疫抑制级联反应，其中 HBV 产生抑制性单核细胞，继而启动调节性 NK 细胞分化，导致 T 细胞抑制。
