An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid.
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.
Chamaillard
Mathias
M
Department of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Hashimoto
Masahito
M
Horie
Yasuo
Y
Masumoto
Junya
J
Qiu
Su
S
Saab
Lisa
L
Ogura
Yasunori
Y
Kawasaki
Akiko
A
Fukase
Koichi
K
Kusumoto
Shoichi
S
Valvano
Miguel A
MA
Foster
Simon J
SJ
Mak
Tak W
TW
Nuñez
Gabriel
G
Inohara
Naohiro
N
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*
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