乙型肝炎病毒不会干扰人体肝脏的天然免疫反应

StephenW

Hepatitis B Virus Does Not Interfere With Innate Immune Responses in the Human Liver
Aleksei Suslov
, Tujana Boldanova
, Xueya Wang
, Stefan Wieland'Correspondence information about the author Stefan Wieland§,Email the author Stefan Wieland
, Markus H. Heim'Correspondence information about the author Markus H. Heim§,Email the author Markus H. Heim
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DOI: https://doi.org/10.1053/j.gastro.2018.01.034 |

Background & Aims

Most viruses are detected at early stages of cell infection and induce an innate immune response mediated by production of 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 polymerase chain reaction, in situ hybridization, HBV RNA quantification, and HBV genotyping; some specimens were incubated with toll-like receptor (TLR) ligands (polyinosinic-polycytidylic acid) 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.
Keywords:
PRR, Virus Immune Evasion, PAMP, Ex Vivo

StephenW

乙型肝炎病毒不会干扰人体肝脏的天然免疫反应
阿列克谢苏斯洛夫
，Tujana Boldanova
，王雪雅
，Stefan Wieland'关于作者StefanWieland§的回复信息“，通过电子邮件发送作者Stefan Wieland
，Markus H. Heim'关于作者Markus H.Heim§的回复信息，通过电子邮件发送给作者Markus H. Heim
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DOI：https：//doi.org/10.1053/j.gastro.2018.01.034 |

背景和目的

大多数病毒在细胞感染的早期阶段被检测到并诱导由干扰素（IFN）产生介导的先天性免疫反应。 IFN诱导数百个IFN刺激基因（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）未检测到HBV，或者由于HBV通过模式识别受体进行检测而抑制IFN产生或信号传导，HBV可能不会诱导先天性免疫应答。我们研究了来自慢性HBV感染不同阶段的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

我们在收集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（大多数患有脂肪肝疾病）后10分钟内获得肝脏。通过组织学，免疫组织化学，定量逆转录聚合酶链式反应，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（聚肌苷酸 - 胞壁酸）一起温育或用仙台病毒感染并分析。
结果

来自HBV感染患者的肝脏标本未表达比对照患者更多的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IFN并且在用poly（I：C）或仙台病毒感染激活TLR3后诱导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感染患者的肝组织没有诱导先天性免疫应答，但是这种应答可以由HBV感染的肝组织中的其他因子（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。
关键词：
PRR，病毒免疫逃避，PAMP，前体

StephenW

https://www.gastrojournal.org/ar ... a4=Gastroenterology