Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Front Immunol. 2022 Jul 29;13:965018. doi: 10.3389/fimmu.2022.965018. eCollection 2022.
Chronic hepatitis B virus (HBV) infection remains to be a substantial global burden, especially for end-stage liver diseases. It is well accepted that HBV-specific T and B cells are essential for controlling HBV infection. Toll-like receptors (TLRs) represent one of the major first-line antiviral defenses through intracellular signaling pathways that induce antiviral inflammatory cytokines and interferons, thereby shaping adaptive immunity. However, HBV has evolved strategies to counter TLR responses by suppressing the expression of TLRs and blocking the downstream signaling pathways, thus limiting HBV-specific adaptive immunity and facilitating viral persistence. Recent studies have stated that stimulation of the TLR signaling pathway by different TLR agonists strengthens host innate immune responses and results in suppression of HBV replication. In this review, we will discuss how TLR-mediated responses shape HBV-specific adaptive immunity as demonstrated in different experimental models. This information may provide important insight for HBV functional cure based on TLR agonists as immunomodulators.
慢性乙型肝炎病毒 (HBV) 感染仍然是一个重大的全球负担，尤其是对于终末期肝病患者而言。人们普遍认为，HBV 特异性 T 细胞和 B 细胞对于控制 HBV 感染至关重要。Toll 样受体 (TLR) 通过细胞内信号通路代表主要的一线抗病毒防御机制之一，该通路可诱导抗病毒炎症细胞因子和干扰素，从而塑造适应性免疫。然而，HBV 通过抑制 TLR 的表达和阻断下游信号通路来进化出对抗 TLR 反应的策略，从而限制 HBV 特异性适应性免疫并促进病毒持续存在。最近的研究表明，不同 TLR 激动剂刺激 TLR 信号通路可增强宿主固有免疫反应，并导致 HBV 复制受到抑制。在这篇综述中，我们将讨论 TLR 介导的反应如何在不同的实验模型中塑造 HBV 特异性适应性免疫。这些信息可能为基于 TLR 激动剂作为免疫调节剂的 HBV 功能性治愈提供重要的见解。
