NOD-LRR Proteins: Role in Host-microbial Interactions and Inflammatory Disease

Nods are cytosolic proteins that contain a nucleotide-binding oligomerization domain (NOD). These proteins include key regulators of apoptosis and pathogen resistance in mammals and plants. A large number of Nods contain leucine-rich repeats (LRRs), hence referred to as NOD-LRR proteins. Genetic variation in several NOD-LRR proteins, including human Nod2, Cryopyrin, and CIITA, as well as mouse Naip5, is associated with inflammatory disease or increased susceptibility to microbial infections. Nod1, Nod2, Cryopyrin, and Ipaf have been implicated in protective immune responses against pathogens. Together with Toll-like receptors, Nod1 and Nod2 appear to play important roles in innate and acquired immunity as sensors of bacterial components. Specifically, Nod1 and Nod2 participate in the signaling events triggered by host recognition of specific motifs in bacterial peptidoglycan and, upon activation, induce the production of proinflammatory mediators. Naip5 is involved in host resistance to Legionella pneumophila through cell autonomous mechanisms, whereas CIITA plays a critical role in antigen presentation and development of antigen-specific T lymphocytes. Thus, NOD-LRR proteins appear to be involved in a diverse array of processes required for host immune reactions against pathogens.