Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
Chin Med J (Engl). 2018 Jan 5;131(1):43-49. doi: 10.4103/0366-6999.221275.
Plasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection.
The healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-β1 and TGF-β2, were performed using Luminex multiplex technology.
In this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-β1, and TGF-β2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05).
This study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.
浆细胞样树突状细胞(pDC)和细胞因子在乙型肝炎病毒(HBV)感染的发生和恢复中起着重要作用。本研究旨在探讨急性或慢性 HBV 感染患者 pDC 的频率和功能以及血清细胞因子网络谱。
本研究纳入了健康个体(HI 组)、免疫耐受(IT)期 HBeAg 阳性慢性 HBV 患者(IT 组)、HBeAg 阳性慢性 HBV 患者(CHB 组)和急性 HBV 患者(AHB 组)。通过流式细胞仪检测 CD86+ pDC 的频率和 pDC 表面 CD86 分子的计数。采用 Luminex 多重技术定量测定 Fms 样酪氨酸激酶 3 配体(Flt-3L)、干扰素(IFN)-α2、IFN-γ、白细胞介素(IL)-17A、IL-6、IL-10、转化生长因子(TGF)-β1 和 TGF-β2 的含量。
本研究中 HI 组 13 例,IT 组 30 例,CHB 组 50 例,AHB 组 32 例。与 HI 组相比,HBV 感染组(包括 IT、CHB 和 AHB 组的所有患者)pDC 表面 CD86 分子的计数明显升高(4596.5±896.5 比 7097.7±3124.6;P<0.001)。CHB 组 pDC 表面 CD86 分子的计数(7739.2±4125.4)明显高于 IT 组(6393.4±1653.6,P=0.043)。与 IT 组相比,CHB 组 Flt-3L、IFN-γ和 IL-17A 的细胞因子谱减少,IFN-α2 明显增加(P=0.012)。与 IT 组和 CHB 组相比,AHB 组 IL-10、TGF-β1 和 TGF-β2 的含量明显增加(均 P<0.05)。
本研究表明 HBV 感染时 pDC 的功能不受影响。增强的 pDC 功能和 IFN-α2 可能参与了 HBV 感染从 IT 期到肝炎活动期的免疫反应触发。急性患者主要表现为通过增强的 IL-10 和 TGF-β 下调免疫反应。