HBV 感染中的细胞因子和趋化因子

StephenW

HBV 感染中的细胞因子和趋化因子
世红钟 1 , 张天灵 1 , 荔波堂 1 , 李永印 1
隶属关系
联系

    1
    中国广州，南方医科大学南方医院感染科，器官衰竭研究国家重点实验室，广东省病毒性肝炎研究重点实验室。

    PMID：34926586 PMCID：PMC8674621 DOI：10.3389/fmolb.2021.805625

抽象的

慢性乙型肝炎病毒 (HBV) 感染仍然是肝脏炎症和损伤的主要原因。慢性乙型肝炎 (CHB) 感染的发病机制主要由持续性肝内免疫病理学介导。肝脏具有独特的解剖学和免疫学结构特征，也被认为是一个免疫器官，在发病条件下会产生大量细胞因子和趋化因子，对HBV感染的进展具有重要意义。肝内先天免疫系统是细胞因子和趋化因子的强大来源，后者也来自肝实质细胞。此外，全身细胞因子和趋化因子随着病程而受到干扰。由于 HBV 是一种隐形病毒，持续暴露于 HBV 相关抗原会导致免疫衰竭，其中调节细胞被肝内趋化因子和细胞因子（包括白细胞介素 10 和转化生长因子 β）募集，参与了此类一系列因果事件。尽管干扰素和核苷（酸）类似物这两种已获批准的治疗方法具有相当大的价值，可以有效抑制 HBV 复制，但它们都不足以使免疫学磨损状态的最佳恢复以赢得功能性或病毒学治愈之战。 CHB 感染。值得注意的是，细胞因子和趋化因子在调节免疫反应中起着至关重要的作用。它们通过直接作用于 HBV 或间接操纵目标免疫细胞来发挥作用。因此，具有作为新型免疫干预措施的潜在可能性的特定细胞因子和趋化因子与针对病毒本身的那些相结合，似乎在治愈 CHB 感染中具有广阔的前景。在这里，我们系统地回顾了最近的文献，这些文献阐明了细胞因子和趋化因子介导的 HBV 感染的发病机制和免疫衰竭及其由当前主流抗 HBV 治疗引发的动力学。疾病进展或控制的预测价值以及特定主要细胞因子和趋化因子在 CHB 感染中的免疫治疗目标也将被描绘出来。

关键词：趋化因子；细胞因子；乙型肝炎病毒;免疫反应;肝病。

版权所有 © 2021 钟、张、唐和李。

StephenW

Cytokines and Chemokines in HBV Infection
Shihong Zhong  1 , Tianling Zhang  1 , Libo Tang  1 , Yongyin Li  1
Affiliations
Affiliation

    1
    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

    PMID: 34926586 PMCID: PMC8674621 DOI: 10.3389/fmolb.2021.805625

Abstract

Chronic hepatitis B virus (HBV) infection remains a leading cause of hepatic inflammation and damage. The pathogenesis of chronic hepatitis B (CHB) infection is predominantly mediated by persistent intrahepatic immunopathology. With the characterization of unique anatomical and immunological structure, the liver is also deemed an immunological organ, which gives rise to massive cytokines and chemokines under pathogenesis conditions, having significant implications for the progression of HBV infection. The intrahepatic innate immune system is responsible for the formidable source of cytokines and chemokines, with the latter also derived from hepatic parenchymal cells. In addition, systemic cytokines and chemokines are disturbed along with the disease course. Since HBV is a stealth virus, persistent exposure to HBV-related antigens confers to immune exhaustion, whereby regulatory cells are recruited by intrahepatic chemokines and cytokines, including interleukin-10 and transforming growth factor β, are involved in such series of causal events. Although the considerable value of two types of available approved treatment, interferons and nucleos(t)ide analogues, effectively suppress HBV replication, neither of them is sufficient for optimal restoration of the immunological attrition state to win the battle of the functional or virological cure of CHB infection. Notably, cytokines and chemokines play a crucial role in regulating the immune response. They exert effects by directly acting on HBV or indirectly manipulating target immune cells. As such, specific cytokines and chemokines, with a potential possibility to serve as novel immunological interventions, combined with those that target the virus itself, seem to be promising prospects in curative CHB infection. Here, we systematically review the recent literature that elucidates cytokine and chemokine-mediated pathogenesis and immune exhaustion of HBV infection and their dynamics triggered by current mainstream anti-HBV therapy. The predictive value of disease progression or control and the immunotherapies target of specific major cytokines and chemokines in CHB infection will also be delineated.

Keywords: chemokine; cytokine; hepatitis B virus; immune response; liver disease.

Copyright © 2021 Zhong, Zhang, Tang and Li.

StephenW

https://www.frontiersin.org/arti ... olb.2021.805625/pdf