TLR2 Ligands
Activation of TLR2-dependent signaling by various ligands
Toll-like receptor 2 (TLR2) plays an essential role in detecting a diverse range of microbial pathogen-associated molecular patterns (PAMPs) from Gram-positive and Gram-negative bacteria as well as fungi, parasites, and viruses. These PAMPs include cell-wall components such as lipoproteins, lipoteichoic acid (LTA; Gram-positive bacteria only), lipoarabinomannan (mycobacteria only), and zymosan (yeast) [1]. TLR2 forms a heterodimer on the cell surface, crucial for signaling and ligand specificity, with co-receptors TLR1 or TLR6. For example, TLR2-TLR1 and TLR2-TLR6 heterodimers are known to bind specific lipoproteins depending on whether they are tri- or diacylated, respectively [2, 3]. Moreover, ligand recognition is enhanced by its non-specific delivery to TLR2 by CD14, and sometimes in combination with additional ligand-specific molecules such as CD36 and Dectin-1 [4, 5].
Upon ligand recognition, TLR2-dependent signaling cascades ultimately lead to a MyD88 and MAL/TIRAP-dependent activation of pro-inflammatory transcription factors such as NF-κB and AP-1 [6]. Additionally, the PI3K/Akt pathway may also be activated leading to the production of anti-inflammatory cytokines [7]. Interestingly, microarray data generated by InvivoGen clearly highlights that downstream effects differ depending on whether it’s the TLR2-TLR1 or TLR2-TLR6 heterodimer that is activated upon ligand recognition.
InvivoGen offers a diverse collection of TLR2 ligands, including:
- Heat killed bacteria- freeze-dried preparations of various bacteria (e.g. E. coli, P. aeruginosa)
- Purified microbial cell-wall components– purified preparations of microbial components (e.g. peptidoglycan, LTA, and zymosan
- Synthetic agonists – chemically synthesized lipoproteins (e.g. Pam3CSK4) and small molecules (i.e. CU-T12-9)
All products are of the highest quality and have been functionally validated in HEK-Blue™ hTLR2 cellular assays.
References:
1. Oliveira-Nascimento, L. et al. 2012. The Role of TLR2 in Infection and Immunity. Front Immunol 3, 79.
2. Takeuchi, O. et al. 2001. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13, 933-940.
3. Takeuchi, O. et al. 2002. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 169, 10-14.
4. Jimenez-Dalmaroni, M.J. et al. 2009. Soluble CD36 ectodomain binds negatively charged diacylglycerol ligands and acts as a co-receptor for TLR2. PLoS One 4, e7411.
5. Lotz, S. et al. 2004. Highly purified lipoteichoic acid activates neutrophil granulocytes and delays their spontaneous apoptosis via CD14 and TLR2. J Leukoc Biol 75, 467-477.
6. Piao, W. et al. 2016. Differential adapter recruitment by TLR2 co-receptors. Pathog Dis 74.
7. Santos-Sierra, S. et al. 2009. Mal connects TLR2 to PI3Kinase activation and phagocyte polarization. EMBO J 28, 2018-2027.