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• W2024458873 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." @default.
• W2024458873 created "2016-06-24" @default.
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• W2024458873 date "2015-01-01" @default.
• W2024458873 modified "2023-10-07" @default.
• W2024458873 title "2'-O-Methylation within Bacterial RNA Acts as Suppressor of TLR7/TLR8 Activation in Human Innate Immune Cells" @default.
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• W2024458873 doi "https://doi.org/10.1159/000375460" @default.
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