title: An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid.
abstract: Nucleotide-binding oligomerization domain protein 1 (NOD1) belongs to a family that includes multiple members with NOD and leucine-rich repeats in vertebrates and plants. NOD1 has been suggested to have a role in innate immune responses, but the mechanism involved remains unknown. Here we report that NOD1 mediates the recognition of peptidoglycan derived primarily from Gram-negative bacteria. Biochemical and functional analyses using highly purified and synthetic compounds indicate that the core structure recognized by NOD1 is a dipeptide, gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP). Murine macrophages deficient in NOD1 did not secrete cytokines in response to synthetic iE-DAP and did not prime the lipopolysaccharide response. Thus, NOD1 mediates selective recognition of bacteria through detection of iE-DAP-containing peptidoglycan.
authors.affiliation: Department of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Mathias
authors.initials: M
authors.lastname: Chamaillard
authors.forename: Masahito
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Horie
authors.forename: Junya
authors.initials: J
authors.lastname: Masumoto
authors.forename: Su
authors.initials: S
authors.lastname: Qiu
authors.forename: Lisa
authors.initials: L
authors.lastname: Saab
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ogura
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valvano
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foster
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nuñez
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003960:Diaminopimelic Acid / Q000378:metabolism*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; D003960:Diaminopimelic Acid