Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST), Nara 630-0192, Japan; Life Science Collaboration Center (LiSCo), Nara Institute of Science and Technology (NAIST), Nara 630-0192, Japan.
Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST), Nara 630-0192, Japan.
Immunity. 2024 Apr 9;57(4):649-673. doi: 10.1016/j.immuni.2024.03.004.
Toll-like receptors (TLRs) are an evolutionarily conserved family in the innate immune system and are the first line of host defense against microbial pathogens by recognizing pathogen-associated molecular patterns (PAMPs). TLRs, categorized into cell surface and endosomal subfamilies, recognize diverse PAMPs, and structural elucidation of TLRs and PAMP complexes has revealed their intricate mechanisms. TLRs activate common and specific signaling pathways to shape immune responses. Recent studies have shown the importance of post-transcriptional regulation in TLR-mediated inflammatory responses. Despite their protective functions, aberrant responses of TLRs contribute to inflammatory and autoimmune disorders. Understanding the delicate balance between TLR activation and regulatory mechanisms is crucial for deciphering their dual role in immune defense and disease pathogenesis. This review provides an overview of recent insights into the history of TLR discovery, elucidation of TLR ligands and signaling pathways, and their relevance to various diseases.
toll 样受体 (TLRs) 是先天免疫系统中进化保守的家族,通过识别病原体相关分子模式 (PAMPs) ,是宿主防御微生物病原体的第一道防线。TLRs 分为细胞表面和内体亚家族,可识别多种 PAMPs,TLRs 和 PAMP 复合物的结构阐明揭示了它们复杂的机制。TLRs 激活共同和特定的信号通路来塑造免疫反应。最近的研究表明,在 TLR 介导体液免疫反应中,转录后调控的重要性。尽管它们具有保护功能,但 TLR 的异常反应导致炎症和自身免疫性疾病。理解 TLR 激活和调节机制之间的微妙平衡对于阐明它们在免疫防御和疾病发病机制中的双重作用至关重要。这篇综述概述了 TLR 发现的历史、TLR 配体和信号通路的阐明,以及它们与各种疾病的相关性的最新进展。