Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
Cell Mol Life Sci. 2022 Oct 12;79(11):547. doi: 10.1007/s00018-022-04582-x.
Toll-like receptors (TLRs) comprise a class of highly conserved molecules that recognize pathogen-associated molecular patterns and play a vital role in host defense against multiple viral infectious diseases. Although TLRs are highly expressed on innate immune cells and play indirect roles in regulating antiviral adaptive immune responses, intrinsic expression of TLRs in adaptive immune cells, including T cells and B cells, cannot be ignored. TLRs expressed in CD4 + and CD8 + T cells play roles in enhancing TCR signal-induced T-cell activation, proliferation, function, and survival, serving as costimulatory molecules. Gene knockout of TLR signaling molecules has been shown to diminish antiviral adaptive immune responses and affect viral clearance in multiple viral infectious animal models. These results have highlighted the critical role of TLRs in the long-term immunological control of viral infection. This review summarizes the expression and function of TLR signaling pathways in T and B cells, focusing on the in vitro and vivo mechanisms and effects of intrinsic TLR signaling in regulating T- and B-cell responses during viral infection. The potential clinical use of TLR-based immune regulatory drugs for viral infectious diseases is also explored.
Toll 样受体(TLRs)是一类高度保守的分子,能够识别病原体相关分子模式,在宿主抵御多种病毒感染性疾病方面发挥着重要作用。尽管 TLRs 在先天免疫细胞上高度表达,并在调节抗病毒适应性免疫反应中发挥间接作用,但 TLRs 在适应性免疫细胞(包括 T 细胞和 B 细胞)中的固有表达不容忽视。CD4+和 CD8+T 细胞中表达的 TLR 能够增强 TCR 信号诱导的 T 细胞激活、增殖、功能和存活,充当共刺激分子。TLR 信号分子的基因敲除已被证明会减弱抗病毒适应性免疫反应,并影响多种病毒感染动物模型中的病毒清除。这些结果强调了 TLR 在病毒感染的长期免疫控制中的关键作用。本综述总结了 TLR 信号通路在 T 细胞和 B 细胞中的表达和功能,重点探讨了固有 TLR 信号在调节病毒感染过程中 T 细胞和 B 细胞反应的体外和体内机制和效应。还探讨了 TLR 为基础的免疫调节药物在病毒感染性疾病中的潜在临床应用。