Zhang Zhikuan, Ohto Umeharu, Shimizu Toshiyuki
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
FEBS Lett. 2017 Oct;591(20):3167-3181. doi: 10.1002/1873-3468.12749. Epub 2017 Jul 21.
The history of mankind has been plagued by the tug of war with viral infections. Toll-like receptors (TLRs) and other receptors of the innate immune system constitute an early defense system against invading viruses by recognizing the viral genetic material, the nucleic acids (NAs). Agonistic ligands of NA-sensing TLRs play an emerging role in the treatment of viral diseases, demonstrating a crucial role of these receptors. Recently, crystal structures have afforded new insights into TLR recognition of NAs. An aberrant activation by self-NAs, which leads to the inflammation and autoimmunity, is avoided by strict regulation of NA-TLR interaction at multiple check-points. This Review summarizes the novel structural understanding of NA-sensing by TLRs and regulatory mechanisms of these receptors.
人类历史一直饱受与病毒感染的斗争之苦。Toll样受体（TLRs）和先天免疫系统的其他受体通过识别病毒遗传物质——核酸（NAs），构成了抵御入侵病毒的早期防御系统。NA感应TLRs的激动剂配体在病毒性疾病治疗中发挥着越来越重要的作用，表明了这些受体的关键作用。最近，晶体结构为TLRs对NAs的识别提供了新的见解。通过在多个检查点严格调控NA-TLR相互作用，避免了自身NAs的异常激活，而这种异常激活会导致炎症和自身免疫。本综述总结了对TLRs感应NAs的新结构理解以及这些受体的调控机制。
