Pattern-recognition receptors (TLR2, TLR9, NOD1, NOD2) (PRRs (TLR2, TLR9, NOD1, NOD2))

This target group comprises four distinct Pattern-recognition receptors (PRRs) essential for innate immunity: Toll-like receptor 2 (TLR2), Toll-like receptor 9 (TLR9), Nucleotide-binding oligomerization domain-containing protein 1 (NOD1), and Nucleotide-binding oligomerization domain-containing protein 2 (NOD2). TLR2 and TLR9 are transmembrane proteins that detect extracellular or endosomal pathogen-associated molecular patterns (PAMPs) such as bacterial lipoproteins and CpG DNA motifs, respectively (UniProt P67948, Q9NR96). NOD1 and NOD2 are intracellular sensors that recognize bacterial peptidoglycan derivatives within the cytoplasm (UniProt Q9Y239, Q9HC29). Activation of these receptors initiates signaling pathways, notably NF-kappaB and MAPK, which drive the expression of pro-inflammatory cytokines and chemokines. While vital for host defense, aberrant signaling is implicated in various pathologies, including inflammatory bowel disease (IBD), asthma, and cancer. Pharmacological modulation includes agonists used as vaccine adjuvants or in cancer immunotherapy to stimulate the immune system, and antagonists being explored to mitigate chronic inflammation and autoimmune responses. These receptors represent a bridge between innate and adaptive immunity, making them versatile targets for diverse therapeutic areas.

Other names

Toll-like receptor 2Toll-like receptor 9Nucleotide-binding oligomerization domain-containing protein 1Nucleotide-binding oligomerization domain-containing protein 2CD282CD289CARD4CARD15TLRsNLRs

Agonism of these receptors (e.g., TLR9 agonists, NOD2 agonists) is used to stimulate innate immunity for oncology or vaccine adjuvancy, while antagonism (e.g., TLR2 antibodies) is employed to suppress pathological inflammation in autoimmune or autoinflammatory conditions.