Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA. Krüger, A., Oldenburg, M., Chebrolu, C., Beisser, D., Kolter, J., Sigmund, A. M., Steinmann, J., Schäfer, S., Hochrein, H., Rahmann, S., Wagner, H., Henneke, P., Hornung, V., Buer, J., & Kirschning, C. J. EMBO Reports, 16(12):1656–1663, Dec, 2015. ![Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 1 download Toll-like receptor (TLR) 13 and TLR2 are the major sensors of Gram-positive bacteria in mice. TLR13 recognizes Sa19, a specific 23S ribosomal (r) RNA-derived fragment and bacterial modification of Sa19 ablates binding to TLR13, and to antibiotics such as erythromycin. Similarly, RNase A-treated Staphylococcus aureus activate human peripheral blood mononuclear cells (PBMCs) only via TLR2, implying single-stranded (ss) RNA as major stimulant. Here, we identify human TLR8 as functional TLR13 equivalent that promiscuously senses ssRNA. Accordingly, Sa19 and mitochondrial (mt) 16S rRNA sequence-derived oligoribonucleotides (ORNs) stimulate PBMCs in a MyD88-dependent manner. These ORNs, as well as S. aureus-, Escherichia coli-, and mt-RNA, also activate differentiated human monocytoid THP-1 cells, provided they express TLR8. Moreover, Unc93b1(-/-)- and Tlr8(-/-)-THP-1 cells are refractory, while endogenous and ectopically expressed TLR8 confers responsiveness in a UR/URR RNA ligand consensus motif-dependent manner. If TLR8 function is inhibited by suppression of lysosomal function, antibiotic treatment efficiently blocks bacteria-driven inflammatory responses in infected human whole blood cultures. Sepsis therapy might thus benefit from interfering with TLR8 function.
@Article{Kruger2015,
author = {Anne Kr\"{u}ger and Marina Oldenburg and Chiranjeevi Chebrolu and Daniela Beisser and Julia Kolter and Anna M. Sigmund and J\"{o}rg Steinmann and Simon Sch\"{a}fer and Hubertus Hochrein and Sven Rahmann and Hermann Wagner and Philipp Henneke and Veit Hornung and Jan Buer and Carsten J. Kirschning},
journal = {EMBO Reports},
title = {Human {T}{L}{R}8 senses {U}{R}/{U}{R}{R} motifs in bacterial and mitochondrial {R}{N}{A}},
year = {2015},
month = {Dec},
number = {12},
pages = {1656--1663},
volume = {16},
abstract = {Toll-like receptor (TLR) 13 and TLR2 are the major sensors of Gram-positive bacteria in mice. TLR13 recognizes Sa19, a specific 23S ribosomal (r) RNA-derived fragment and bacterial modification of Sa19 ablates binding to TLR13, and to antibiotics such as erythromycin. Similarly, RNase A-treated Staphylococcus aureus activate human peripheral blood mononuclear cells (PBMCs) only via TLR2, implying single-stranded (ss) RNA as major stimulant. Here, we identify human TLR8 as functional TLR13 equivalent that promiscuously senses ssRNA. Accordingly, Sa19 and mitochondrial (mt) 16S rRNA sequence-derived oligoribonucleotides (ORNs) stimulate PBMCs in a MyD88-dependent manner. These ORNs, as well as S. aureus-, Escherichia coli-, and mt-RNA, also activate differentiated human monocytoid THP-1 cells, provided they express TLR8. Moreover, Unc93b1(-/-)- and Tlr8(-/-)-THP-1 cells are refractory, while endogenous and ectopically expressed TLR8 confers responsiveness in a UR/URR RNA ligand consensus motif-dependent manner. If TLR8 function is inhibited by suppression of lysosomal function, antibiotic treatment efficiently blocks bacteria-driven inflammatory responses in infected human whole blood cultures. Sepsis therapy might thus benefit from interfering with TLR8 function.},
doi = {10.15252/embr.201540861},
keywords = {paper},
url = {http://dx.doi.org/10.15252/embr.201540861},
}
Downloads: 1
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