IL-12p70 in Primary Human Monocytes versus TLR8 and to Induce High Amounts of of RNA Oligonucleotides to Activate TLR7 Selection of Molecular Structure and Delivery
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TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation.
Dendritic cells (DCs) play an important role in bridging innate and adaptive immunity. These APCs have the ability to recognize specific molecular signatures of pathogens through TLRs. In particular, the intracellular TLR7 and TLR8, mediating the recognition of ssRNA by DCs, play a major role in the immune response during viral infection. Although differences have been identified between TLR7 a...
متن کاملIdentification of RNA sequence motifs stimulating sequence-specific TLR8-dependent immune responses.
The TLRs 7, 8, and 9 stimulate innate immune responses upon recognizing pathogen nucleic acids. U-rich RNA sequences were recently discovered that stimulate human TLR7/8-mediated or murine TLR7-mediated immune effects. In this study we identified single-stranded RNA sequences containing defined sequence motifs that either preferentially activate human TLR8-mediated as opposed to TLR7- or TLR7/8...
متن کاملOligodeoxynucleotides differentially modulate activation of TLR7 and TLR8 by imidazoquinolines.
Among the 11 human TLRs, a subfamily TLR7, TLR8, and TLR9 display similarities in structure and endosomal localization. Natural agonists consisting of nucleic acids, such as ssRNA or DNA with CpG motifs, activate the innate immune cells through these TLRs. Immune response modifiers (IRMs) of imidazoquinoline class compounds 3M-001, 3M-002, and 3M-003 have been shown to activate the innate immun...
متن کاملRNA and imidazoquinolines are sensed by distinct TLR7/8 ectodomain sites resulting in functionally disparate signaling events.
TLRs 7 and 8 are pattern recognition receptors controlling antiviral host defense or autoimmune diseases. Apart from foreign and host RNA, synthetic RNA oligoribonucleotides (ORN) or small molecules of the imidazoquinoline family activate TLR7 and 8 and are being developed as therapeutic agonists. The structure-function relationships for RNA ORN and imidazoquinoline sensing and consequent downs...
متن کاملHuman dendritic cells stimulated via TLR7 and/or TLR8 induce the sequential production of Il-10, IFN-gamma, and IL-17A by naive CD4+ T cells.
Depending upon which TLRs are triggered, dendritic cells (DCs) may orient the differentiation of naive CD4(+) T cells toward either Th1, Th2, regulatory T cells, or the recently defined Th17 lineage. In this study, we report that a dual stimulation of TLR4 and TLR7/8 with LPS plus R848 leads human monocyte-derived DCs (MoDCs) to produce multiple pro- and anti-inflammatory cytokines, including I...
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