Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA
Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA
Immunity 23, 165-175 (2005) 1
Speaker: 鄭自勝 Time: 14:10-15:00, May 24, 2006
Commentator: 凌斌 老師 Place: Room 601
Abstract:
The innate immune system is the first line of defense against invading pathogens. It utilizes Toll-like receptors (TLRs) to recognize conserved pathogen-associated molecular patterns (PAMPs). Several TLRs recognize and respond to nucleic acids, such as DNA, dsRNA, and ssRNA recognized by TLR9, TLR3, and TLR7 and TLR8, respectively 2. The reason for why only bacterial DNA is immunogenic, not mammalian, is unmethylated CpG motif acting upon TLR9 on immune cells. Previously, the authors have demonstrated that RNA which is transcribed in vitro or released from necrotic mammalian cells can activate human dendritic cells (DCs), whereas eukaryotic mRNA and tRNA cannot 3. In this report, the authors first established that RNA is a ligand for human TLRs. Next, they used RNA bearing modified nucleosides to suppress the capacity of RNA to activate cytokine-generated DCs, and found that distinct TLRs responded differently to RNA that contained different modified nucleosides. Finally, they demonstrated that RNA-mediated immune stimulation was suppressed proportionally with the number of modified nucleosides present in RNA and that even a few modifications were sufficient to exert a suppressive effect. Taken together, innate immune system may detect RNA lacking nucleoside modification as a means of selectively responding to bacteria or necrotic tissue.
References:
1. Kariko, K. et al. (2005) Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165-175.
2. Akira, S. and Takeda, K. (2004) Toll-like receptor signaling. Nat. Rev. Immunol. 4, 499–511.
3. Kariko, K. et al. (2004) mRNA is an endogenous ligand for Toll-like receptor 3. J. Biol. Chem. 279, 12542–12550.