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Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan
Stephen E. Girardin,1Ivo G. Boneca,2*Leticia A. M. Carneiro,3*Aude Antignac,4Muguette Jéhanno,3Jérôme Viala,3Karsten Tedin,5Muhamed-Kheir Taha,4Agnès Labigne,2Ulrich Zäthringer,6Anthony J. Coyle,7Peter S. DiStefano,7John Bertin,7Philippe J. Sansonetti,1Dana J. Philpott3
Although the role of Toll-like receptors in extracellular bacterialsensing has been investigated intensively, intracellular detectionof bacteria through Nod molecules remains largely uncharacterized.Here, we show that human Nod1 specifically detects a uniquediaminopimelate-containing N-acetylglucosamine–N-acetylmuramicacid (GlcNAc-MurNAc) tripeptide motif found in Gram-negativebacterial peptidoglycan, resulting in activation of the transcriptionfactor NF-B pathway. Moreover, we show that in epithelial cells(which represent the first line of defense against invasivepathogens), Nod1is indispensable for intracellular Gram-negativebacterial sensing.
1 Unité de Pathogénie Microbienne Moléculaire, INSERM U389, Institut Pasteur, 28, Rue du Dr. Roux, 75724Paris Cedex 15, France. 2 Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, 28, Rue du Dr. Roux, 75724Paris Cedex 15, France. 3 Groupe d'Immunité Innée et Signalisation, Institut Pasteur, 28, Rue du Dr. Roux, 75724Paris Cedex 15, France. 4 Unité des Neisseria, Institut Pasteur, 28, Rue du Dr. Roux, 75724Paris Cedex 15, France. 5 Institut für Mikrobiologie und Tierseuchen, Freie Universität Berlin, Philippstrasse 13, D-10115 Berlin, Germany. 6 Division of Immunochemistry, Research Center Borstel, Center for Medicine and Biosciences, D-23845 Borstel, Germany. 7 Millennium Pharmaceuticals Inc., Cambridge, MA 02139 USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: philpott{at}pasteur.fr
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Community-Based Safety, Immunogenicity, and Transmissibility Study of the Shigella sonnei WRSS1 Vaccine in Israeli Volunteers.
N. Orr, D. E. Katz, J. Atsmon, P. Radu, M. Yavzori, T. Halperin, T. Sela, R. Kayouf, Z. Klein, R. Ambar, et al. (2005)
Infect. Immun.
73, 8027-8032
|Abstract »|Full Text »|PDF »
Peptidoglycan recognition by the Drosophila Imd pathway.
T. Kaneko, D. Golenbock, and N. Silverman (2005)
Innate Immunity
11, 383-389
|Abstract »|PDF »
How Toll-like receptors and Nod-like receptors contribute to innate immunity in mammals.
J. H. Fritz and S. E. Girardin (2005)
Innate Immunity
11, 390-394
|Abstract »|PDF »
Identification of the Critical Residues Involved in Peptidoglycan Detection by Nod1.
S. E. Girardin, M. Jehanno, D. Mengin-Lecreulx, P. J. Sansonetti, P. M. Alzari, and D. J. Philpott (2005)
J. Biol. Chem.
280, 38648-38656
|Abstract »|Full Text »|PDF »
IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1{beta} and IL-6 production through a caspase 1-dependent mechanism.
M. G. Netea, T. Azam, G. Ferwerda, S. E. Girardin, M. Walsh, J.-S. Park, E. Abraham, J.-M. Kim, D.-Y. Yoon, C. A. Dinarello, et al. (2005)
PNAS
102, 16309-16314
|Abstract »|Full Text »|PDF »
Nod1 Participates in the Innate Immune Response to Pseudomonas aeruginosa.
L. H. Travassos, L. A. M. Carneiro, S. E. Girardin, I. G. Boneca, R. Lemos, M. T. Bozza, R. C. P. Domingues, A. J. Coyle, J. Bertin, D. J. Philpott, et al. (2005)
J. Biol. Chem.
280, 36714-36718
|Abstract »|Full Text »|PDF »
Selective Recognition of Synthetic Lysine and meso-Diaminopimelic Acid-type Peptidoglycan Fragments by Human Peptidoglycan Recognition Proteins I{alpha} and S.
S. Kumar, A. Roychowdhury, B. Ember, Q. Wang, R. Guan, R. A. Mariuzza, and G.-J. Boons (2005)
J. Biol. Chem.
280, 37005-37012
|Abstract »|Full Text »|PDF »
Peptidoglycan Recognition Protein 2 (N-Acetylmuramoyl-L-Ala Amidase) Is Induced in Keratinocytes by Bacteria through the p38 Kinase Pathway.
H. Wang, D. Gupta, X. Li, and R. Dziarski (2005)
Infect. Immun.
73, 7216-7225
|Abstract »|Full Text »|PDF »
Peptidoglycan degradation by specialized lytic transglycosylases associated with type III and type IV secretion systems.
D. Zahrl, M. Wagner, K. Bischof, M. Bayer, B. Zavecz, A. Beranek, C. Ruckenstuhl, G. E. Zarfel, and G. Koraimann (2005)
Microbiology
151, 3455-3467
|Abstract »|Full Text »|PDF »
Epithelial Cells and Their Neighbors. IV. Bacterial contributions to intestinal epithelial barrier integrity.
A. S. Ismail and L. V. Hooper (2005)
Am J Physiol Gastrointest Liver Physiol
289, G779-G784
|Abstract »|Full Text »|PDF »
Pattern Recognition Molecules Activated by Chlamydia muridarum Infection of Cloned Murine Oviduct Epithelial Cell Lines.
W. A. Derbigny, M. S. Kerr, and R. M. Johnson (2005)
J. Immunol.
175, 6065-6075
|Abstract »|Full Text »|PDF »
B 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. 
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