NOD1

NOD1, also known as NLRC1, is a cytosolic pattern recognition receptor in the NOD-like receptor (NLR) family that detects intracellular bacterial components and contributes to the innate immune response. It is expressed in a range of cell types, including epithelial and myeloid cells, and plays a role in orchestrating host defense and maintaining mucosal homeostasis.

Structure and function: NOD1 contains a caspase activation and recruitment domain (CARD) at the N terminus, a central nucleotide-binding and oligomerization domain (NACHT), and a C-terminal series of leucine-rich repeats (LRRs) that regulate ligand sensing and autoregulation. Upon detection of its ligand, NOD1 oligomerizes and recruits downstream signaling molecules.

Ligand recognition: NOD1 recognizes a peptidoglycan motif called iE-DAP (gamma-D-glutamyl-meso-diaminopimelic acid), commonly found in the cell walls of many Gram-negative bacteria and some Gram-positive organisms. Recognition triggers receptor activation.

Signaling and responses: Activated NOD1 engages the serine/threonine kinase RIPK2 via CARD–CARD interactions, leading to activation of NF-κB and MAP kinase pathways and the transcription of proinflammatory cytokines and chemokines such as IL-6, IL-8, and TNF-α. NOD1 signaling can also promote autophagy by recruiting ATG16L1 to sites of bacterial entry, aiding bacterial clearance.

Clinical relevance: NOD1 participates in antibacterial defense and shaping intestinal microbiota. Genetic variation in NOD1 has been studied in relation to inflammatory diseases, including Crohn’s disease and other inflammatory bowel conditions, but associations are nuanced and not as strong as those observed for NOD2.