Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan.
Although the role of Toll-like receptors in extracellular bacterial sensing has been investigated intensively, intracellular detection of bacteria through Nod molecules remains largely uncharacterized. Here, we show that human Nod1 specifically detects a unique diaminopimelate-containing N-acetylglucosamine-N-acetylmuramic acid (GlcNAc-MurNAc) tripeptide motif found in Gram-negative bacterial peptidoglycan, resulting in activation of the transcription factor NF-kappaB pathway. Moreover, we show that in epithelial cells (which represent the first line of defense against invasive pathogens), Nod1is indispensable for intracellular Gram-negative bacterial sensing.
Girardin
Stephen E
SE
Unité de Pathogénie Microbienne Moléculaire, INSERM U389, Institut Pasteur, 28, Rue du Dr. Roux, 75724Paris Cedex 15, France.
Boneca
Ivo G
IG
Carneiro
Leticia A M
LA
Antignac
Aude
A
Jéhanno
Muguette
M
Viala
Jérôme
J
Tedin
Karsten
K
Taha
Muhamed-Kheir
MK
Labigne
Agnes
A
Zähringer
Ulrich
U
Coyle
Anthony J
AJ
DiStefano
Peter S
PS
Bertin
John
J
Sansonetti
Philippe J
PJ
Philpott
Dana J
DJ
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003593:Cytoplasm / Q000382:microbiology; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006090:Gram-Negative Bacteria / Q000737:chemistry* / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D009842:Oligopeptides / Q000032:analysis* / Q000737:chemistry; D010457:Peptidoglycan / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D014312:Trisaccharides / Q000032:analysis* / Q000737:chemistry
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D002352:Carrier Proteins; C474832:GM-tripeptide, Neisseria meningitidis; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D009842:Oligopeptides; D010457:Peptidoglycan; D011971:Receptors, Immunologic; D014312:Trisaccharides