Toll-like receptor 2, Toll-like receptor 4, Toll-like receptor 5 (TLR2/4/5)

Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), and Toll-like receptor 5 (TLR5) are key cell-surface proteins belonging to the pattern recognition receptor (PRR) family. These receptors are specialized to detect pathogen-associated molecular patterns (PAMPs) from bacteria and other microbes; specifically, TLR2 recognizes lipoproteins, TLR4 identifies Gram-negative bacterial lipopolysaccharide (LPS), and TLR5 senses bacterial flagellin. Upon activation, they trigger intracellular signaling cascades through adaptor proteins like MyD88 and TRIF, leading to the activation of the NF-kappaB transcription factor and the subsequent release of pro-inflammatory cytokines. These receptors are involved in the pathogenesis of various conditions, including sepsis, chronic inflammatory diseases, autoimmune disorders, and cancer. Pharmacological intervention targeting these receptors includes the development of TLR agonists as vaccine adjuvants or anti-tumor agents, such as entolimod and monophosphoryl lipid A, as well as TLR antagonists like eritoran and resatorvid to control excessive inflammatory responses. Therapeutic challenges include the risk of inducing systemic cytokine storms or compromising the host's ability to defend against infections.

Other names

TLR2TLR4TLR5CD282CD284CD285Toll-like receptorsTIL4ARMD10

Modulation (agonism or antagonism) of cell-surface Toll-like receptors to regulate innate immune signaling via the MyD88- and TRIF-dependent pathways.