Diebold Sandra S
King's College London, 2nd Floor Borough Wing, Peter Gorer Department of Immunobiology, Guy's Hospital, London SE1 9RT, United Kingdom.
Adv Drug Deliv Rev. 2008 Apr 29;60(7):813-23. doi: 10.1016/j.addr.2007.11.004. Epub 2007 Dec 27.
The Toll-like receptors (TLR), mediating innate immune activation upon recognition of viral nucleic acids, represent promising targets for the development of adjuvants. Therefore, there is great interest in unraveling the underlying mechanisms of ligand recognition. Studies aiming to identify which sequences, nucleic acid modifications and molecular moieties of viral nucleic acids trigger or inhibit TLR activation have allowed insights into this subject, yet there are still many aspects of innate recognition of viral nucleic acids which are only partially understood. This review discusses our current understanding of TLR-mediated recognition of viral single-stranded RNA (ssRNA) by TLR7 and TLR8. Oligoribonucleotides (ORN) and small immune response modifiers such as imidazoquinolines with agonist function have served as tools to study ligand recognition. In addition, there is increasing evidence that TLR-mediated recognition of mammalian ssRNA triggers innate immune activation and plays a role in autoimmunity. Thus the development of suitable TLR7 and TLR8 antagonists could pave the way for therapeutic intervention of particular autoimmune diseases.
Toll样受体(TLR)在识别病毒核酸后介导天然免疫激活,是开发佐剂的有前景的靶点。因此,人们对揭示配体识别的潜在机制非常感兴趣。旨在确定病毒核酸的哪些序列、核酸修饰和分子部分触发或抑制TLR激活的研究,使人们对这一主题有了深入了解,但病毒核酸天然识别的许多方面仍仅得到部分理解。本综述讨论了我们目前对TLR7和TLR8介导的病毒单链RNA(ssRNA)识别的理解。寡核糖核苷酸(ORN)和具有激动剂功能的咪唑喹啉等小免疫反应调节剂已作为研究配体识别的工具。此外,越来越多的证据表明,TLR介导的哺乳动物ssRNA识别触发天然免疫激活,并在自身免疫中起作用。因此,开发合适的TLR7和TLR8拮抗剂可为特定自身免疫性疾病的治疗干预铺平道路。