Lin You-Sheng, Chang Yung-Chi, Pu Tzu-Yu, Chuang Tsung-Hsien, Hsu Li-Chung
Institute of Molecular Medicine, National Taiwan University, No 7, Chung Shan S. Rd., Taipei, 10002, Taiwan.
Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
J Biomed Sci. 2025 Jun 10;32(1):56. doi: 10.1186/s12929-025-01151-9.
The innate immune system is the host's initial response to eliminate pathogens and repair tissue damage. Innate immune cells, such as macrophages and dendritic cells, use pattern recognition receptors (PRRs) to recognize microbial structures and stress-induced molecules released from dead or damaged cells, thereby initiating immune responses. Among PRRs, Toll-like receptors (TLRs) are well-studied and are located either on the cell surface or in endosomal compartments. Most endosomal TLRs specifically recognize nucleic acids and are thus referred to as nucleic acid (NA)-sensing TLRs. Upon activation, these receptors induce the production of inflammatory cytokines and type I interferons and initiate subsequent adaptive immunity. These immune responses work to suppress pathogens and inhibit tumor growth. However, excessive cytokine and interferon production can lead to various inflammatory diseases. This review focuses on mammalian nucleic acid-sensing TLRs, summarizing the molecular regulation of their activations, the impact of their dysregulation on human diseases, and therapeutic strategies that target these TLRs.
固有免疫系统是宿主消除病原体和修复组织损伤的初始反应。固有免疫细胞，如巨噬细胞和树突状细胞，利用模式识别受体（PRR）来识别微生物结构以及从死亡或受损细胞释放的应激诱导分子，从而启动免疫反应。在PRR中，Toll样受体（TLR）得到了充分研究，它们位于细胞表面或内体区室。大多数内体TLR特异性识别核酸，因此被称为核酸（NA）传感TLR。激活后，这些受体诱导炎性细胞因子和I型干扰素的产生，并启动随后的适应性免疫。这些免疫反应有助于抑制病原体和抑制肿瘤生长。然而，细胞因子和干扰素的过度产生会导致各种炎症性疾病。本综述聚焦于哺乳动物核酸传感TLR，总结其激活的分子调控、失调对人类疾病的影响以及针对这些TLR的治疗策略。
