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- W3048665493 abstract "Surface-exposed Toll-like receptors (TLRs) such as TLR2 and TLR4 survey the extracellular environment for pathogens. TLR activation initiates the production of various cytokines and chemokines, including type I interferons (IFN-I). Downstream of TLR4, IFNβ secretion is only vigorously triggered in macrophages when the receptor undergoes endocytosis and switches signaling adaptor; surface TLR4 engagement predominantly induces proinflammatory cytokines via the signaling adaptor MyD88. It is unclear whether this dichotomy is generally applicable to other TLRs, cell types, or differentiation states. Here, we report that diverse TLR2 ligands induce an IFN-I response in human monocyte-like cells, but not in differentiated macrophages. This TLR2-dependent IFN-I signaling originates from the cell surface and depends on MyD88; it involves combined activation of the transcription factors IRF3 and NF-κB, driven by the kinases TBK1 and TAK1-IKKβ, respectively. TLR2-stimulated monocytes produced modest IFNβ levels that caused productive downstream signaling, reflected by STAT1 phosphorylation and expression of numerous interferon-stimulated genes. Our findings reveal that the outcome of TLR2 signaling includes an IFN-I response in human monocytes, which is lost upon macrophage differentiation, and differs mechanistically from IFN-I-induction through TLR4. These findings point to molecular mechanisms tailored to the differentiation state of a cell and the nature of receptors activated to control and limit TLR-triggered IFN-I responses." @default.
- W3048665493 created "2020-08-18" @default.
- W3048665493 creator A5012740226 @default.
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- W3048665493 creator A5069627449 @default.
- W3048665493 creator A5076608963 @default.
- W3048665493 creator A5081422502 @default.
- W3048665493 date "2020-10-01" @default.
- W3048665493 modified "2023-10-12" @default.
- W3048665493 title "An alternative model for type I interferon induction downstream of human TLR2" @default.
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- W3048665493 doi "https://doi.org/10.1074/jbc.ra120.015283" @default.
- W3048665493 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7573265" @default.
- W3048665493 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32796029" @default.
- W3048665493 hasPublicationYear "2020" @default.