Department of Immunology, University of Toronto, Toronto, ON, Canada; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Department of Immunology, University of Toronto, Toronto, ON, Canada; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Antiviral Res. 2020 Jul;179:104816. doi: 10.1016/j.antiviral.2020.104816. Epub 2020 May 7.
The concept of immune evasion is a longstanding topic of debate during chronic Hepatitis B Virus infection. The 292 million individuals chronically infected by HBV are clear evidence that the virus avoids elimination by the immune system. The exact mechanisms of immune evasion remain undefined and are distinct, but likely interconnected, between innate and adaptive immunity. There is a significant body of evidence that supports peripheral tolerance and exhaustion of adaptive immunity but our understanding of the role that central tolerance plays is still developing. Innate immunity instructs the adaptive immune response and subversion of its functionality will impact both T and B cell responses. However, literature around the interaction of HBV with innate immunity is inconsistent, with reports suggesting that HBV avoids innate recognition, suppresses innate recognition, or activates innate immunity. This complexity has led to confusion and controversy. This review will discuss the mechanisms of central and peripheral tolerance/exhaustion of adaptive immunity in the context of chronic HBV infection. We also cover the interaction of HBV with cells of the innate immune system and propose concepts for the heterogeneity of responses in chronically infected patients.
免疫逃逸是慢性乙型肝炎病毒感染过程中一个长期存在的争论话题。2.92 亿慢性乙型肝炎病毒感染者清楚地表明，病毒逃避了免疫系统的清除。免疫逃逸的确切机制尚不清楚，先天免疫和适应性免疫之间存在明显但可能相互关联的区别。有大量证据支持外周耐受和适应性免疫衰竭，但我们对中枢耐受所起作用的理解仍在不断发展。先天免疫指导适应性免疫反应，其功能的颠覆将影响 T 细胞和 B 细胞反应。然而，关于乙型肝炎病毒与先天免疫相互作用的文献并不一致，有报道称乙型肝炎病毒逃避先天识别、抑制先天识别或激活先天免疫。这种复杂性导致了困惑和争议。本综述将讨论慢性乙型肝炎病毒感染中适应性免疫的中枢和外周耐受/衰竭的机制。我们还涵盖了乙型肝炎病毒与先天免疫细胞的相互作用，并为慢性感染患者的异质性反应提出了概念。
