2'-O-methylation within bacterial RNA acts as suppressor of TLR7/TLR8 activation in human innate immune cells

• Verfasst von: Rimbach, Katharina [VerfasserIn]
• Verfasst von: Kaiser, Steffen [VerfasserIn]
• Verfasst von: Helm, Mark [VerfasserIn]
• Verfasst von: Dalpke, Alexander [VerfasserIn]
• Verfasst von: Eigenbrod, Tatjana [VerfasserIn]
• Titel: 2'-O-methylation within bacterial RNA acts as suppressor of TLR7/TLR8 activation in human innate immune cells
• Verf.angabe: Katharina Rimbach, Steffen Kaiser, Mark Helm, Alexander H. Dalpke, Tatjana Eigenbrod
• E-Jahr: 2015
• Jahr: March 20, 2015
• Umfang: 12 S.
• Fussnoten: Gesehen am 25.06.2020
• Titel Quelle: Enthalten in: Journal of innate immunity
• Ort Quelle: Basel : Karger, 2009
• Jahr Quelle: 2015
• Band/Heft Quelle: 7(2015), 5, Seite 482-493
• ISSN Quelle: 1662-8128
• DOI: doi:10.1159/000375460
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1702126471

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 <i>Escherichia coli</i> tRNA^Tyr 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^Tyr as a universal suppressor of innate immune activation in the human but not the murine system.