Journal
JOURNAL OF INNATE IMMUNITY
Volume 10, Issue 5-6, Pages 398-406Publisher
KARGER
DOI: 10.1159/000494034
Keywords
Endosome; Extracellular RNA; Innate immune signaling; RNA uptake; Toll-like receptor
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Funding
- Japan Agency for Medical Research and Development [16nk0101327h0002]
- Akiyama Life Science Foundation
- Uehara Memorial Foundation
- Alexander von Humboldt Foundation
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RNA works as a genome and messenger in RNA viruses, and it sends messages in most of the creatures of the Earth, including viruses, bacteria, fungi, plants, and animals. The human innate immune system has evolved to detect single-and double-stranded RNA molecules from microbes by pattern recognition receptors and induce defense reactions against infections such as the production of type I interferons and inflammatory cytokines. To avoid cytokine toxicity causing chronic inflammation or autoimmunity by sensing self-RNA, the activation of RNA sensors is strictly regulated. All of the Toll-like receptors that recognize RNA are localized to endosomes/lysosomes, which require internalization of RNA for sensing through an endocytic pathway. RIG-I-like receptors sense RNA in cytosol. These receptors are expressed in a cell type-specific fashion, enabling sensing of RNA for a wide range of microbial invasions. At the same time, both endosomal and cytoplasmic receptors have strategies to respond only to RNA of pathogenic microorganisms or dying cells. RNA are potential vaccine adjuvants for immune enhancement against cancer and provide a benefit for vaccina-tions. Understanding the detailed molecular mechanisms of the RNA-sensing system will help us to broaden the clinical utility of RNA adjuvants for patients with incurable diseases. (c) 2018 S. Karger AG, Basel
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