Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) (TLR2/4)

Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) are essential pattern recognition receptors (PRRs) predominantly expressed on antigen-presenting cells (APCs) like macrophages and dendritic cells (UniProt O60603, P33767). These receptors are pivotal in the innate immune response, where TLR4 recognizes lipopolysaccharide (LPS) from Gram-negative bacteria and TLR2 identifies lipopeptides and peptidoglycan from Gram-positive bacteria (StatPearls, NBK526068). Activation of these receptors triggers signaling pathways, such as the MyD88 and TRIF pathways, resulting in the production of pro-inflammatory cytokines and the maturation of APCs (PubMed, PMID: 25035065). In clinical contexts, overactivation of TLR2/4 is linked to systemic inflammatory response syndrome (SIRS), sepsis, and various autoimmune conditions (NIH Gene ID: 7099, 7097). Therapeutic strategies include the use of TLR4 antagonists like Eritoran and Resatorvid (TAK-242) to mitigate sepsis-related inflammation, as well as TLR4 agonists like Monophosphoryl lipid A (MPLA) which serve as potent vaccine adjuvants (PubChem CID: 11254400, 114969). However, targeting these receptors presents challenges, including the risk of inducing a cytokine storm with agonists or increasing susceptibility to infections with antagonists (Journal of Leukocyte Biology, PMID: 21159999).

Other names

CD282CD284TLR2TLR4TIL4hToll

Antagonism of TLR4 or TLR2 to inhibit pro-inflammatory signaling; Agonism of TLR4 to stimulate innate immune responses and act as a vaccine adjuvant.