Toll-like receptors (TLR) 7 and 8 are involved in the responses to viral and some bacterial infections. TLR7 and 8 display a high degree of similarity at the level of sequence as well as functionality. Both receptor types are located in the endosomal compartment and recognize single-stranded (ss) RNAs. Upon recognition of ssRNA, the TLR7/8 pathway is initiated via recruitment of MYD88 (myeloid differentiation primary response 88). The signaling cascade finally leads to the activation of the transcription factors NF-κB, AP-1, and/or IRF-7. Thus, the expression of pro-inflammatory cytokines and type I IFNs is triggered, which initiates the immune response. Apart from naturally occurring ligands, TLR7 and 8 can be activated by receptor agonists, like synthetic RNA oligoribonucleotides (ORNs) or small synthetic molecules of the imidazoquinoline family.
We provide high-quality ORNs for activation of either TLR7 only, TLR8 only, or TLR7 and TLR8 simultaneously, together with the respective controls. The control ORNs do not activate TLR7 or TLR8 and can serve as controls for backbone- or transfection reagent–related effects. We also offer the synthetic small molecule R848 (Resiquimod), which activates TLR7 and TLR8.
TLR7 and TLR8 are expressed differently in human and mouse immune cells. In humans, TLR7 is predominantly present in plasmacytoid dendritic cells (pDCs) and B cells, whereas in mice also myeloid dendritic cells (mDCs) and monocytes express the receptor. In contrast, TLR8 is highly expressed in human myeloid cells, but appears to be absent in pDCs. The functionality of TLR8 in mice is controversially discussed as the receptor has been suggested to be non-functional or counteracting TLR7.
Choose between TLR7, TLR8, or TLR7/8 agonists, depending on which receptor or immune cell type you want to activate:
Table 1: Overview of available products with respective target cells.
|Product group||Product||Sequence / molecular structure||Target receptor expression / target cells|
|TLR7 only||Agonist||ORN R-2336||rG-rA-rC-rA-rC-rA-rC-rA-rC-rA-rC-rU-rC-rA-rC-rA-rC-rA-rC-rA-rC-rA-rC-rA||human: TLR7 is predominantly expressed in pDCs and B cells.|
mouse: TLR7 is also expressed in myeloid cells.
|Control ORN||ORN R-2336 Control||rG-rA-rC-rA-rC-rA-rC-rA-rC-rA-rC-rA-rC-rA-rC-rA-rC-rA-rC-rA-rC-rA-rC-rU|
|TLR8 only||Agonist||ORN R-0002||rU*rU*rA*rU*rU*rA*rU*rU*rA*rU*rU*rA*rU* rU*rA*rU*rU*rA*rU*rU||human: TLR8 is mainly expressed in cells of the myeloid lineage, such as monocytes, macrophages, and mDCs.|
|Control ORN||ORN R-1263 (control for ORN R-0002 and ORN R-0006)||rG*rC*rC*rA*rC*rC*rG*rA*rG*rC*rC*rG*rA* rA*rG*rG*rC*rA*rC*rC|
|TLR7 and TLR8||Agonists||ORN R-0006||rU*rU*rG*rU*rU*rG*rU*rU*rG*rU*rU*rG*rU* rU*rG*rU*rU*rG*rU*rU||TLR7/8 agonists activate both human TLR7 and TLR8, as well as murine TLR7.|
|ORN RNA 40||rG*rC*rC*rC*rG*rU*rC*rU*rG*rU*rU*rG*rU* rG*rU*rG*rA*rC*rU*rC|
|ORN R-2176-dT||rU*rU*rG*rU*rU*rG*rU*rU*rG*rU*rU*rG*rU* rU*rG*rU*dG*dG*dG*dG*dG*dT|
|Control ORNs||ORN 1263 (control for |
ORN R-0002 and ORN R-0006)
|ORN RNA 41 (control for RNA 40)||rG*rC*rC*rC*rG*rA*rC*rA*rG*rA*rA*rG*rA* rG*rA*rG*rA*rC*rA*rC|
|ORN R-2176-dT Control||rA*rA*rG*rA*rA*rG*rA*rA*rG*rA*rA*rG*rA*rA* rG*rA*dG*dG*dG*dG*dG*dT|
Interested in getting a comprehensive package of different TLR7/8 ligands?
Have a look at our TLR7/8 Explorer. The kit comprises three different TLR7/8 agonists for stimulation of either TLR7 (ORN R-2336), TLR8 (ORN R-0002), or both, TLR7 and TLR8 simultaneously (ORN R-0006). Also, the suitable control ORNs are included in the kit: ORN R-1263 (as control for ORN R-0002 and ORN R-0006) and ORN R-2336 control.
To enable ORN uptake and protect the sensitive RNA from degradation, ORNs need to be formulated with cationic lipids. The recommended transfection reagent is DOTAP-Cl (1,2-Dioleoyloxy-3-trimethyl-ammonium-propane chloride). An overview about the stimulatory capacities of TLR7/8 agonists with and without transfection reagent is given in table 2.
Table 2: Stimulatory capacities of TLR7/8 agonists with and without transfection reagent.
All ORNs are delivered with transfection reagent and protocol to enable easy, safe, and fast experimental set-up. ORN R-21798-dT, exclusively available from Miltenyi Biotec, can also be used without prior complexation to DOTAP, further simplifying cell activation.
Keep in mind to use suitable negative controls to ensure that observed effects are not caused by backbone or transfection reagent. To identify the suitable control for the ORN of your choice, please have a look at table 1.
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