Sensitization to TLR7 Agonist in IFN-β-Preactivated Dendritic Cells

摘要: TLRs interact with a growing list of pathogen-derived products and these interactions drive the activation innate adaptive immune responses. Dendritic cells (DC) play key role in events expressing heterogeneous repertoire TLRs. We have previously demonstrated production type I IFNs DC following bacterial infections TLR triggering. In this study, we sought to characterize transcriptome specifically induced human by IFN-β stimulated upon LPS treatment. To aim, using cDNA microarrays, compared treatment absence or presence neutralizing anti-type IFN Abs. Interestingly, found that expression TLR7 was during LPS-induced maturation IFN-dependent manner. The induction maturing mainly consequence transcriptional activity IRF-1, whose binding site located within promoter. Moreover, also “priming” immature DC, usually express TLR8 but not TLR7, exogenous functionally active TLR7. fact, TLR7-specific ligand 3M-001 up-regulated CD83, CD86, CD38 IFN-β-primed DC. Therefore, robust enhancement proinflammatory as well regulatory cytokines observed. These data suggest TLR4-mediated release activates specific transcription programs amplifying pathogen sensors correctly combinatorially respond viral infection.