2′-O-Methylation within Bacterial RNA Acts as Suppressor of TLR7/TLR8 Activation in Human Innate Immune Cells
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Katharina Rimbach
- Steffen Kaiser
- Mark Helm
- Alexander H Dalpke
- Tatjana Eigenbrod
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000360469300006&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1159/000375460
- eISSN
- 1662-8128
- Externe Identifier
- Clarivate Analytics Document Solution ID: CQ2YU
- PubMed Identifier: 25823462
- ISSN
- 1662-811X
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- JOURNAL OF INNATE IMMUNITY
- Schlüsselwörter
- Bacterial RNA
- RNA modification
- 2 '-O-methylation
- Immunostimulation
- Innate immunity
- Peripheral blood mononuclear cells
- Paginierung
- 482 - 493
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Titel
- 2′-O-Methylation within Bacterial RNA Acts as Suppressor of TLR7/TLR8 Activation in Human Innate Immune Cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 7
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:p>Microbial RNA is an important stimulator of innate immune responses. Differences in posttranscriptional RNA modification profiles enable the immune system to discriminate between self and non-self nucleic acids. This principle may be exploited by certain bacteria to circumvent immune cell activation. In this regard, 2'-O-methylation of <i>Escherichia coli</i> tRNA<sup>Tyr</sup> at position 18 (Gm18) has recently been described to inhibit TLR7-mediated IFN-a production in human plasmacytoid dendritic cells (pDCs). Extending these findings, we now demonstrate that Gm18 also potently inhibits TLR7-independent human monocyte activation by RNA derived from a variety of bacterial strains. The half minimal inhibitory concentration values were similar to those found for IFN-a inhibition in pDCs. Mechanistically, 2'-O-methylated RNA impaired upstream signalling events, including MAP kinase and NF&#954;B activation. Our results suggest that antagonizing effects of Gm18-modified RNA are due to competition with stimulatory RNA for receptor binding. The antagonistic effect was specific for RNA because the small molecule TLR7/8 agonist R848 was not inhibited. Despite the striking phenotype in human cells, 2'-O-methylated RNA did not interfere with TLR13 activation by bacterial 23S rRNA in murine DC and BMDM. Thus, we identify here Gm18 in <i>E. coli</i> tRNA<sup>Tyr</sup> as a universal suppressor of innate immune activation in the human but not the murine system.</jats:p>
- Autoren
- Katharina Rimbach
- Steffen Kaiser
- Mark Helm
- Alexander H Dalpke
- Tatjana Eigenbrod
- DOI
- 10.1159/000375460
- eISSN
- 1662-8128
- ISSN
- 1662-811X
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- Journal of Innate Immunity
- Sprache
- en
- Online publication date
- 2015
- Paginierung
- 482 - 493
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Herausgeber
- S. Karger AG
- Herausgeber URL
- http://dx.doi.org/10.1159/000375460
- Datum der Datenerfassung
- 2024
- Titel
- 2'-O-Methylation within Bacterial RNA Acts as Suppressor of TLR7/TLR8 Activation in Human Innate Immune Cells
- Ausgabe der Zeitschrift
- 7
Datenquelle: Crossref
- Abstract
- Microbial RNA is an important stimulator of innate immune responses. Differences in posttranscriptional RNA modification profiles enable the immune system to discriminate between self and non-self nucleic acids. This principle may be exploited by certain bacteria to circumvent immune cell activation. In this regard, 2'-O-methylation of Escherichia coli tRNATyr at position 18 (Gm18) has recently been described to inhibit TLR7-mediated IFN-α production in human plasmacytoid dendritic cells (pDCs). Extending these findings, we now demonstrate that Gm18 also potently inhibits TLR7-independent human monocyte activation by RNA derived from a variety of bacterial strains. The half minimal inhibitory concentration values were similar to those found for IFN-α inhibition in pDCs. Mechanistically, 2'-O-methylated RNA impaired upstream signalling events, including MAP kinase and NFx03BA;B activation. Our results suggest that antagonizing effects of Gm18-modified RNA are due to competition with stimulatory RNA for receptor binding. The antagonistic effect was specific for RNA because the small molecule TLR7/8 agonist R848 was not inhibited. Despite the striking phenotype in human cells, 2'-O-methylated RNA did not interfere with TLR13 activation by bacterial 23S rRNA in murine DC and BMDM. Thus, we identify here Gm18 in E. coli tRNA(Tyr) as a universal suppressor of innate immune activation in the human but not the murine system.
- Addresses
- Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany.
- Autoren
- Katharina Rimbach
- Steffen Kaiser
- Mark Helm
- Alexander H Dalpke
- Tatjana Eigenbrod
- DOI
- 10.1159/000375460
- eISSN
- 1662-8128
- Externe Identifier
- PubMed Identifier: 25823462
- PubMed Central ID: PMC6738864
- Open access
- false
- ISSN
- 1662-811X
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- Journal of innate immunity
- Schlüsselwörter
- Dendritic Cells
- Monocytes
- Cells, Cultured
- Animals
- Mice, Inbred Strains
- Humans
- Mice
- Escherichia coli
- Extracellular Signal-Regulated MAP Kinases
- NF-kappa B
- Interferon-alpha
- RNA, Bacterial
- Signal Transduction
- Species Specificity
- Methylation
- Toll-Like Receptor 7
- Toll-Like Receptor 8
- Immunity, Innate
- Immunosuppression Therapy
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2015
- Paginierung
- 482 - 493
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum der Datenerfassung
- 2015
- Titel
- 2'-O-Methylation within Bacterial RNA Acts as Suppressor of TLR7/TLR8 Activation in Human Innate Immune Cells.
- Sub types
- Comparative Study
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 7
Files
https://www.karger.com/Article/Pdf/375460 https://europepmc.org/articles/PMC6738864?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- Microbial RNA is an important stimulator of innate immune responses. Differences in posttranscriptional RNA modification profiles enable the immune system to discriminate between self and non-self nucleic acids. This principle may be exploited by certain bacteria to circumvent immune cell activation. In this regard, 2'-O-methylation of Escherichia coli tRNATyr at position 18 (Gm18) has recently been described to inhibit TLR7-mediated IFN-α production in human plasmacytoid dendritic cells (pDCs). Extending these findings, we now demonstrate that Gm18 also potently inhibits TLR7-independent human monocyte activation by RNA derived from a variety of bacterial strains. The half minimal inhibitory concentration values were similar to those found for IFN-α inhibition in pDCs. Mechanistically, 2'-O-methylated RNA impaired upstream signalling events, including MAP kinase and NFx03BA;B activation. Our results suggest that antagonizing effects of Gm18-modified RNA are due to competition with stimulatory RNA for receptor binding. The antagonistic effect was specific for RNA because the small molecule TLR7/8 agonist R848 was not inhibited. Despite the striking phenotype in human cells, 2'-O-methylated RNA did not interfere with TLR13 activation by bacterial 23S rRNA in murine DC and BMDM. Thus, we identify here Gm18 in E. coli tRNA(Tyr) as a universal suppressor of innate immune activation in the human but not the murine system.
- Date of acceptance
- 2015
- Autoren
- Katharina Rimbach
- Steffen Kaiser
- Mark Helm
- Alexander H Dalpke
- Tatjana Eigenbrod
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/25823462
- DOI
- 10.1159/000375460
- eISSN
- 1662-8128
- Externe Identifier
- PubMed Central ID: PMC6738864
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- J Innate Immun
- Schlüsselwörter
- Animals
- Cells, Cultured
- Dendritic Cells
- Escherichia coli
- Extracellular Signal-Regulated MAP Kinases
- Humans
- Immunity, Innate
- Immunosuppression Therapy
- Interferon-alpha
- Methylation
- Mice
- Mice, Inbred Strains
- Monocytes
- NF-kappa B
- RNA, Bacterial
- Signal Transduction
- Species Specificity
- Toll-Like Receptor 7
- Toll-Like Receptor 8
- Sprache
- eng
- Country
- Switzerland
- Paginierung
- 482 - 493
- PII
- 000375460
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2016
- Titel
- 2'-O-Methylation within Bacterial RNA Acts as Suppressor of TLR7/TLR8 Activation in Human Innate Immune Cells.
- Sub types
- Comparative Study
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 7
Datenquelle: PubMed
- Beziehungen:
- Eigentum von