Sequence specific detection of bacterial 23S ribosomal RNA by TLR13.
Sequence specific detection of bacterial 23S ribosomal RNA by TLR13.
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DOI：
10.7554/elife.00102
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发表时间：
2012-10-30
期刊：
影响因子：
7.7
通讯作者：
Chen ZJ
中科院分区：
文献类型：
--
作者：
Li XD;Chen ZJ
Toll-like receptors (TLRs) detect microbial infections and trigger innate immune responses. Among vertebrate TLRs, the role of TLR13 and its ligand are unknown. Here we show that TLR13 detects the 23S ribosomal RNA of both gram-positive and gram-negative bacteria. A sequence containing 13 nucleotides near the active site of 23S rRNA ribozyme, which catalyzes peptide bond synthesis, was both necessary and sufficient to trigger TLR13-dependent interleukin-1β production. Single point mutations within this sequence destroyed the ability of the 23S rRNA to stimulate the TLR13 pathway. Knockout of TLR13 in mice abolished the induction of interleukin-1β and other cytokines by the 23S rRNA sequence. Thus, TLR13 detects bacterial RNA with exquisite sequence specificity. DOI: http://dx.doi.org/10.7554/eLife.00102.001 A central feature of the immune system is the ability to detect bacteria, viruses and other pathogens so that they can be repelled or neutralized before they cause lasting damage to an organism. Cells employ a number of different receptors that can detect these pathogens or the molecules they produce. Many of these are called pattern recognition receptors because they recognize certain signatures of microorganisms such as nucleic acids or carbohydrates. An important class of pattern recognition receptor is the toll-like receptor: there are many different families of the receptors, each recognizing a unique feature of bacteria or viruses. (The word toll, which means ‘great’ in German, refers to a gene whose mutations lead to striking phenotypes in flies, and has nothing to do with road and bridge tolls.) Toll-like receptors have two parts that perform two different functions: when one part binds the relevant microbial molecules, the other part sends a signal that results in the production of effector proteins. These proteins include interleukin-1β, which helps to fight infection by causing the inflammation of tissue. To date, 12 different types of toll-like receptors have been found in mice, including three—known as TLR11, TLR12 and TLR13—that are not present in humans. Very little is known about the functions of TLR12 and TLR13. Humans, on the other hand, possess 10 different TLRs, only one of which, TLR10, is not found in mice. Li and Chen have now discovered that TLR13 is responsible for detecting a certain type of ribosomal RNA called 23S ribosomal RNA that are present in bacteria but not in eukaryotic cells. Moreover, they have shown that a short sequence of 13 residues within the 23S ribosomal RNA triggers this pathway and leads to the production of interleukin-1β. The sequence of 13 residues is located at an active site in the RNA that catalyzes the synthesis of peptide bonds, and changing just one of these residues stops the production of interleukin-1β. Other forms of ribosomal RNA are unable to trigger the production of interleukin-1β. These results show that TLR13 differs from all other pattern recognition receptors because it is able to recognize a specific RNA sequence. Li and Chen went on to generate mice lacking TLR13 and showed that immune cells isolated from these mice failed to respond to bacterial RNA. These mice can be used to investigate the role of TLR13 in immune responses to bacterial infections in vivo. DOI: http://dx.doi.org/10.7554/eLife.00102.002
