Bertheloot Damien, Naumovski Allison L, Langhoff Pia, Horvath Gabor L, Jin Tengchuan, Xiao Tsan Sam, Garbi Natalio, Agrawal Sudhir, Kolbeck Roland, Latz Eicke
Institute of Innate Immunity, University Hospital, University of Bonn, 53127 Bonn, Germany.
MedImmune LLC, Gaithersburg, MD 20878.
J Immunol. 2016 Nov 15;197(10):4118-4126. doi: 10.4049/jimmunol.1502169. Epub 2016 Oct 19.
Nucleic acid recognition is an important mechanism that enables the innate immune system to detect microbial infection and tissue damage. To minimize the recognition of self-derived nucleic acids, all nucleic acid-sensing signaling receptors are sequestered away from the cell surface and are activated in the cytoplasm or in endosomes. Nucleic acid sensing in endosomes relies on members of the TLR family. The receptor for advanced glycation end-products (RAGE) was recently shown to bind DNA at the cell surface, facilitating DNA internalization and subsequent recognition by TLR9. In this article, we show that RAGE binds RNA molecules in a sequence-independent manner and enhances cellular RNA uptake into endosomes. Gain- and loss-of-function studies demonstrate that RAGE increases the sensitivity of all ssRNA-sensing TLRs (TLR7, TLR8, TLR13), suggesting that RAGE is an integral part of the endosomal nucleic acid-sensing system.
核酸识别是一种重要机制，可使先天免疫系统检测微生物感染和组织损伤。为了尽量减少对自身来源核酸的识别，所有核酸传感信号受体都被隔离在细胞表面之外，并在细胞质或内体中被激活。内体中的核酸传感依赖于TLR家族成员。晚期糖基化终产物受体（RAGE）最近被证明可在细胞表面结合DNA，促进DNA内化并随后被TLR9识别。在本文中，我们表明RAGE以序列非依赖性方式结合RNA分子，并增强细胞RNA摄取到内体中。功能获得和功能丧失研究表明，RAGE增加了所有单链RNA传感TLR（TLR7、TLR8、TLR13）的敏感性，这表明RAGE是内体核酸传感系统的一个组成部分。
