Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation.
Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation.
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Natural Killer p46 控制乙型肝炎病毒复制并调节肝脏炎症。
DOI：
10.1371/journal.pone.0135874
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Niu J
中科院分区：
文献类型：
--
作者：
Li W;Jiang Y;Wang X;Jin J;Qi Y;Chi X;Zhang H;Feng X;Niu J
自然杀伤（NK）细胞在控制B型肝炎病毒（HBV）感染中起着重要作用，并受到激活和抑制受体的复杂网络的调节。然而，HBV患者的NK细胞活性仍然知之甚少。本研究旨在探讨慢性B型肝炎（CH B）不同感染阶段患者外周血NK细胞的表型和功能特征。我们研究了86例CHB患者和20例健康对照者的NK细胞表型、受体表达和功能。纯化NK细胞，并通过流式细胞术表征NK细胞亚群。检测细胞毒活性（CD 107 a）和干扰素-γ（IFN-γ）分泌，并研究自然杀伤细胞p46（NKP 46）阻断和对K562、HepG 2和HepG2.215细胞系的自发NK细胞溶细胞活性。与其他组相比，非活动性HBsAg携带者的活化NKp 46受体表达更高（p = 0.008）。NKp 46表达与HBV DNA（R =-0.253，p = 0.049）和ALT（R =-0.256，p = 0.045）水平呈负相关。与免疫耐受组相比，免疫活化组中的CD 107 a较高（p = 0.039）。CD 107 a表达与病毒载量（p = 0.02）和HBeAg状态（p = 0.024）相关。体外NKp 46阻断降低了NK细胞对HepG 2和HepG2.215细胞系的细胞溶解活性（p = 0.02; p = 0.039）。此外，来自高病毒载量CHB患者的NK细胞对负载抗NKp 46的K562靶标显示出显著较低的特异性细胞溶解活性（p = 0.0321）。IFN-γ分泌量无显着差异（p > 0.05）。总之，NKp 46表达调节NK细胞的细胞溶解功能。NKp 46可能在HBV复制抑制和HBV相关肝损伤期间调节NK细胞活性，并且可能在CHB感染期间对NK细胞活性至关重要。
Natural killer (NK) cells play an important role in hepatitis B virus (HBV) infection control, and are regulated by a complex network of activating and inhibitory receptors. However, NK cell activity in HBV patients remains poorly understood. The objective of this study was to investigate the phenotypic and functional characteristics of circulating NK cells in patients during different chronic hepatitis B (CHB) infection stages. We investigated NK cell phenotypes, receptor expression and function in 86 CHB patients and 20 healthy controls. NK cells were purified and NK cell subsets were characterized by flow cytometry. Cytotoxic activity (CD107a) and interferon-gamma (IFN-γ) secretion were examined, and Natural Killer p46 (NKP46) blockade and spontaneous NK cell cytolytic activity against K562, HepG2 and HepG2.215 cell lines was studied. Activating NKp46 receptor expression was higher in inactive HBsAg carriers when compared with other groups (p = 0.008). NKp46 expression negatively correlated with HBV DNA (R = -0.253, p = 0.049) and ALT (R = -0.256, p = 0.045) levels. CD107a was higher in immune-activated groups when compared with immune-tolerant groups (p = 0.039). CD107a expression was related to viral load (p = 0.02) and HBeAg status (p = 0.024). In vitro NKp46 blockade reduced NK cell cytolytic activity against HepG2 and HepG2.215 cell lines (p = 0.02; p = 0.039). Furthermore, NK cells from high viral load CHB patients displayed significantly lower specific cytolytic activity against anti-NKp46-loaded K562 targets (p = 0.0321). No significant differences were observed in IFN-γ secretion (p > 0.05). In conclusion, NKp46 expression regulates NK cell cytolytic function. NKp46 may moderate NK cell activity during HBV replication suppression and HBV-associated liver damage and may be critical for NK cell activity during CHB infection.