PT - JOURNAL ARTICLE AU - Haijun Li AU - Naicui Zhai AU - Zhongfeng Wang AU - Hongxiao Song AU - Yang Yang AU - An Cui AU - Tianyang Li AU - Guangyi Wang AU - Junqi Niu AU - Ian Nicholas Crispe AU - Lishan Su AU - Zhengkun Tu TI - Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection AID - 10.1136/gutjnl-2017-314098 DP - 2017 Sep 12 TA - Gut PG - gutjnl-2017-314098 4099 - http://gut.bmj.com/content/early/2017/09/12/gutjnl-2017-314098.short 4100 - http://gut.bmj.com/content/early/2017/09/12/gutjnl-2017-314098.full AB - 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.