Journal
JOURNAL OF IMMUNOLOGY
Volume 197, Issue 10, Pages 4118-4126Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1502169
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Funding
- Immuno-Sensation Cluster
- [Sonderforschungsbereich (SFB 704)]
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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.
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