title: NOD1 and NOD2: signaling, host defense, and inflammatory disease.
abstract: The nucleotide-binding oligomerization domain (NOD) proteins NOD1 and NOD2, the founding members of the intracellular NOD-like receptor family, sense conserved motifs in bacterial peptidoglycan and induce proinflammatory and antimicrobial responses. Here, we discuss recent developments about the mechanisms by which NOD1 and NOD2 are activated by bacterial ligands, the regulation of their signaling pathways, and their role in host defense and inflammatory disease. Several routes for the entry of peptidoglycan ligands to the host cytosol to trigger activation of NOD1 and NOD2 have been elucidated. Furthermore, genetic screens and biochemical analyses have revealed mechanisms that regulate NOD1 and NOD2 signaling. Finally, recent studies have suggested several mechanisms to account for the link between NOD2 variants and susceptibility to Crohn's disease. Further understanding of NOD1 and NOD2 should provide new insight into the pathogenesis of disease and the development of new strategies to treat inflammatory and infectious disorders.
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Caruso
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Warner
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: gabriel.nunez@umich.edu.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D053474:Nod1 Signaling Adaptor Protein / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D000942:Antigens, Bacterial; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; D051192:Receptors, Pattern Recognition