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.
Highlights
Toll-like receptors are evolutionarily conserved transmembrane proteins that detect microbial components on the cell surface or within the endosomes (Takeuchi and Akira, 2010)
Our previous studies showed that transfection of RNA from Lactobacillus salivarius (LAB), a grampositive commensal bacterium commonly found in the gastrointestinal tract, strongly induced IL-1β in mouse bone marrow derived macrophages (BMDM) and Raw264.7, a mouse macrophage cell line (Li et al, 2011)
Because IL-1β induction by LAB RNA depends on MyD88 and Unc93b1, but not other Toll-like receptors (TLRs) known to be involved in single-stranded RNA (ssRNA) detection, we investigated the role of TLR11 family members in detecting bacterial RNA
Summary
Toll-like receptors are evolutionarily conserved transmembrane proteins that detect microbial components on the cell surface or within the endosomes (Takeuchi and Akira, 2010). The TLR1 family includes TLR1, TLR2, TLR6, TLR10 and TLR14, which are localized on the plasma membrane. Within this family, TLR2 forms a heterodimer with other member of the family (e.g., TLR1, TLR6 or TLR10) to detect microbial lipopeptides and peptidoglycans. TLR4, after binding to LPS, can traffic to endosomal membrane where it launches a signaling cascade leading to the production of type-I interferons (IFNα and IFNβ). Members of the remaining TLR families, TLR3, TLR7 and TLR11 are localized on the endosomal membrane. TLR3 detects double-stranded RNA and induces inflammatory cytokines and interferons. 10 TLRs (TLR1–10) have been identified in humans and 12 (TLR1–9, TLR11–13) in mice
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