乙型肝炎病毒不干扰人体肝脏的天然免疫反应

StephenW

Gastroenterology. 2018 Feb 2. pii: S0016-5085(18)30078-7. doi: 10.1053/j.gastro.2018.01.034. [Epub ahead of print]
Hepatitis B Virus Does Not Interfere with Innate Immune Responses in the Human Liver.Suslov A1, Boldanova T2, Wang X1, Wieland S3, Heim MH4.
Author information
1Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland.2Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland; Division of Gastroenterology and Hepatology, University Hospital Basel, Basel CH-4031, Switzerland.3Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland. Electronic address: [email protected].4Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland; Division of Gastroenterology and Hepatology, University Hospital Basel, Basel CH-4031, Switzerland. Electronic address: [email protected].

AbstractBACKGROUND AND AIMS: Most viruses are detected at early stages of cell infection and induce an innate immune response mediated by production interferons (IFNs). IFNs induce expression of hundreds of IFN-stimulated genes (ISGs). Infection of chimpanzees with hepatitis C virus, but not hepatitis B virus (HBV), induces ISG expression in the liver. HBV might not induce an innate immune response because it is not detected by pattern recognition receptors (the stealth properties of HBV) or because HBV suppresses IFN production or signaling despite detection by pattern recognition receptors. We studied innate immune signaling in liver biopsies from patients with different stages of chronic HBV infection and uninfected individuals (controls).
METHODS: We obtained liver within 10 minutes after collection from 30 patients with chronic HBV infection (hepatitis B e antigen-positive or -negative, with or without hepatitis) and 42 controls (most with fatty liver disease). The liver tissues were analyzed by histology, immunohistochemistry, quantitative reverse-transcription PCR, in situ hybridization, HBV RNA quantification, and HBV genotyping; some specimens were incubated with toll-like receptor (TLR) ligands (poly [I:C]) or infected with Sendai virus and then analyzed.
RESULTS: Liver specimens from patients with HBV infection were not expressing more IFN or ISGs than those from control patients, indicating that chronic HBV infection did not activate an innate immune response. However, liver specimens from patients with HBV infection did produce IFN and induce expression of ISGs following activation of TLR3 with poly(I:C) or Sendai virus infections, so the innate immune response is not suppressed in these tissues.
CONCLUSION: Liver tissues from patients with chronic HBV infection do not have induction of an innate immune response, but this response can be activated by other factors (TLR3 binding, Sendai virus infection) in HBV-infected liver tissue. These findings support the hypothesis that HBV is invisible to pattern recognition receptors.

Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

KEYWORDS: PAMP; PRR; ex vivo; virus immune evasion

PMID:29408639DOI:10.1053/j.gastro.2018.01.034

StephenW

消化内科。 2018年2月2日。pii：S0016-5085（18）30078-7。 doi：10.1053 / j.gastro.2018.01.034。 [电子版提前打印]
乙型肝炎病毒不干扰人体肝脏的天然免疫反应。
Suslov A1，Boldanova T2，Wang X1，Wieland S3，Heim MH4。
作者信息

1
    巴塞尔大学巴塞尔大学医院生物医学系，巴塞尔CH-4031，瑞士。
2
    瑞士巴塞尔CH-4031巴塞尔大学巴塞尔大学医院生物医学系;瑞士巴塞尔CH-4031巴塞尔大学医院消化科和肝病科。
3
    巴塞尔大学巴塞尔大学医院生物医学系，巴塞尔CH-4031，瑞士。电子地址：[email protected]。
4
    瑞士巴塞尔CH-4031巴塞尔大学巴塞尔大学医院生物医学系;瑞士巴塞尔CH-4031巴塞尔大学医院消化科和肝病科。电子地址：[email protected]。

抽象
背景和目标：

大多数病毒在细胞感染的早期阶段被检测到并诱导由生产性干扰素（IFN）介导的先天性免疫应答。 IFN诱导数百个IFN刺激的基因（ISG）的表达。黑猩猩感染丙型肝炎病毒，但不感染乙型肝炎病毒（HBV），诱导肝脏中的ISG表达。由于模式识别受体（HBV的隐形性质）没有检测到HBV，或者由于HBV通过模式识别受体检测，抑制IFN产生或信号传导，HBV可能不会诱导先天免疫反应。我们研究了不同阶段慢性HBV感染患者的肝活检组织和未感染的个体（对照）的先天性免疫信号。
方法：

我们从30例慢性HBV感染（乙型肝炎e抗原阳性或阴性，伴或不伴肝炎）患者和42名对照（大部分患有脂肪肝疾病）收集后10分钟内获得了肝脏。通过组织学，免疫组织化学，定量逆转录PCR，原位杂交，HBV RNA定量和HBV基因分型来分析肝组织。将一些标本与Toll样受体（TLR）配体（poly [I：C]）一起温育或用仙台病毒感染，然后分析。
结果：

来自HBV感染患者的肝脏标本不比对照患者表达更多的IFN或ISG，表明慢性HBV感染不激活先天性免疫应答。然而，来自HBV感染患者的肝脏标本确实产生了IFN并且在用poly（I：C）或仙台病毒感染激活TLR3后诱导了ISG的表达，因此在这些组织中先天免疫应答不被抑制。
结论：

来自慢性HBV感染患者的肝组织不具有诱导先天性免疫应答的反应，但是这种反应可以被HBV感染的肝组织中的其它因子（TLR3结合，仙台病毒感染）激活。这些发现支持了HBV对模式识别受体不可见的假设。

版权所有©2018 AGA研究所。由Elsevier Inc.出版。保留所有权利。
关键词：

PAMP; PRR;离体;病毒免疫逃避

结论：
    29408639
DOI：
    10.1053 / j.gastro.2018.01.034

jdcy

路过！

Hepbest

结果：
来自HBV感染患者的肝脏标本不比对照患者表达更多的IFN或ISG，表明慢性HBV感染不激活先天性免疫应答。然而，来自HBV感染患者的肝脏标本确实产生了IFN并且在用poly（I：C）或仙台病毒感染激活TLR3后诱导了ISG的表达，因此在这些组织中先天免疫应答不被抑制。
结论：
来自慢性HBV感染患者的肝组织不具有诱导先天性免疫应答的反应，但是这种反应可以被HBV感染的肝组织中的其它因子（TLR3结合，仙台病毒感染）激活。这些发现支持了HBV对模式识别受体不可见的假设。
——激活先天性免疫，它山之石，可以攻玉

MP4

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