EASL2012:Hepatitis B virus surface antigen suppresses Innate and adaptive immune

StephenW

Abstract               
                                

Title	Hepatitis B virus surface antigen suppresses Innate and adaptive immune responses of murine and human liver cells
Speaker:	Ruth   Bröring
Author:	M. Jiang1, M. Trippler1, R. Broering1*, L. Poggenpohl1, G. Gerken1, M. Lu2, J.F. Schlaak1
Affiliation:	1Department of Gastroenterology and Hepatology, University Hospital of Essen, 2Institute of Virology, University Hospital of Essen, Essen, Germany. *[email protected]
Background and aims: It has recently been shown that Toll-like receptor (TLR) signaling in murine non-parenchymal (NPC) liver cells is suppressed in the presence of Hepatitis B surface antigen (HBsAg). It is not clear, however, whether this is also relevant for adaptive and human immune responses and how this effect is mediated. Methods: Peripheral blood mononuclear cells (PBMCs) from chronic HBV infected patients were stimulated by TLR3 ligands in the absence or presence of autologous serum. Murine Kupffer cells (KC), sinusoidal endothelial cells (LSEC) and hepatocytes as well as human LSEC and hepatocytes were stimulated with TLR3 ligand Poly I:C in the presence or absence of HBsAg. Expression of cytokines and TLR3 was analyzed by quantitative rt-PCR. Mixed lymphocyte reactions (MLR) were performed to study T cell activation induced by TLR-stimulated NPC. Activation of transcription factors was assessed by western blot and reporter gene assays. Results: TLR3-induced production of IFN-γ was suppressed in PBMC from patients with high HBsAg-levels (p< 0.0006) compared to PBMC isolated from patients with low HBsAg-levels. In the presence of autologous serum, TLR3 induced IFN-γ production was inhibited in case of HBV-containing serum. Activation of T lymphocytes which was induced by TLR3-activated NPC was potently suppressed by HBsAg. This suppressive effect was associated with enhanced IL-10 production that could be reverted by IL-10 antibodies. While Poly I:C-induced TLR3 expression remained unchanged, TLR-induced activation of NFκB, IRF-3 and MAPKs was potently suppressed by HBsAg. Conclusions: These findings may, at least in part, explain how HBV evades innate and adaptive immune responses to establish a persistent infection.

StephenW

标题B型肝炎病毒表面抗原抑制小鼠和人类肝细胞的先天免疫和适应性免疫反应
主讲人：露丝Bröring
作者：M.江1，M. Trippler1，R. Broering1 *，M. LU2，L. Poggenpohl1，G. Gerken1，摩根富林明Schlaak1
单位：胃肠病学和肝病学，病毒学，埃森，德国埃森大学医院2Institute埃森大学医院，1Department。 * ruth.broering单向due.de
背景和目的：它最近已表明，Toll样受体（TLR）信号在小鼠非实质（人大）的肝细胞，抑制乙型肝炎表面抗原（HBsAg）的存在。然而，目前尚不清楚这是否也是适应性和人体免疫反应有关，这种效果是如何介导的。
方法：慢性HBV感染患者的外周血单个核细胞（PBMCs）中TLR3的配体在没有或存在自体血清刺激。与TLR3的配聚我：C刺激小鼠库普弗细胞（KC）肝窦内皮细胞（LSEC）和肝细胞以及人类LSEC和肝，乙肝表面抗原的存在或缺乏。细胞因子和TLR3表达的定量RT-PCR分析。混合淋巴细胞反应（MLR），进行了研究由全国人大诱导的TLR刺激T细胞活化。激活转录因子评估印迹和报告基因检测。
结果：PBMC中TLR3的诱导γ-干扰素的生产抑制患者具有较高的HBsAg水平（P <0.0006）相比，PBMC的分离从患者的HBsAg水平低。在自体血清的存在，TLR3的诱导干扰素γ生产中含有乙肝病毒血清的情况下抑制。 potently抑制乙肝表面抗原激活TLR3的活化全国人大诱导的T淋巴细胞。这种抑制作用与增强IL-10 IL-10抗体，可以恢复生产。聚我：C诱导TLR3的表达，而保持不变，TLR为诱导NFκB的活化，IRF-3和蛋白激酶potently抑制乙肝表面抗原。
结论：这些调查结果，至少可以部分解释如何乙肝病毒逃避先天免疫和适应性免疫反应，以建立持久的感染。

咬牙硬挺

rep9ac能清除表抗原，进而自身免疫苏醒清除病毒