Abstract
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.
Keywords:
E. coli; Innate Immunity; Mouse; Ribosomal RNA; Toll-like receptor; bacteria.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Cells, Cultured
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Escherichia coli / chemistry
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Gene Expression
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Immunity, Innate
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Interleukin-1beta / biosynthesis
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Interleukin-1beta / metabolism
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Lactobacillus / chemistry
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / immunology*
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Mice
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Mice, Knockout
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Molecular Sequence Data
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RNA, Bacterial / isolation & purification
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RNA, Bacterial / metabolism*
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RNA, Ribosomal, 23S / isolation & purification
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RNA, Ribosomal, 23S / metabolism*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Toll-Like Receptors / antagonists & inhibitors
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Toll-Like Receptors / genetics*
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Toll-Like Receptors / immunology
Substances
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Interleukin-1beta
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RNA, Bacterial
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RNA, Ribosomal, 23S
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RNA, Small Interfering
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Tlr13 protein, mouse
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Toll-Like Receptors