Nucleotide-binding, oligomerization domain (NOD)-like receptors (NLRs) are a family of cytosolic proteins that play an important role in inflammation and immunity. The NLR family consists of twenty-two human proteins and at least thirty-four mouse proteins that contain a central nucleotide-binding, oligomerization domain (NOD or NACHT), a variable number of C-terminal leucine-rich repeats, and an N-terminal protein interaction domain. Similar to the leucine-rich repeat-containing toll-like receptors (TLRs), multiple NLRs function as pattern recognition receptors. These NLRs are responsible for detecting specific pathogen-associated molecules or host-derived damage signals in the cytosol and initiating the innate immune response.
NOD1/NLRC1 and NOD2/NLRC2 are two pattern recognition receptors that are activated by specific components of bacterial peptidoglycan. Their activation triggers signaling pathways that drive the NF-kappa B-/AP-1-dependent expression of pro-inflammatory cytokines and the IRF3- and/or IRF7-dependent expression of type I interferons. Additionally, activation of NOD1 and NOD2 can induce autophagy through an interaction with Autophagy-related 16-like 1 (ATG16L1). Although a clear connection between NOD1 and chronic inflammatory diseases has not been well-established, mutations in NOD2 have been linked to Crohn’s disease and Blau syndrome.