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Science 300 (5625): 1584-1587

Copyright © 2003 by the American Association for the Advancement of Science

Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan

Stephen E. Girardin,1 Ivo G. Boneca,2* Leticia A. M. Carneiro,3* Aude Antignac,4 Muguette Jéhanno,3 Jérôme Viala,3 Karsten Tedin,5 Muhamed-Kheir Taha,4 Agnès Labigne,2 Ulrich Zäthringer,6 Anthony J. Coyle,7 Peter S. DiStefano,7 John Bertin,7 Philippe J. Sansonetti,1 Dana J. Philpott3{dagger}

Abstract: 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-{kappa}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.

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.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: philpott{at}pasteur.fr


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   Abstract »    Full Text »    PDF »
The Innate Immune Receptor Nod1 Protects the Intestine from Inflammation-Induced Tumorigenesis.
G. Y. Chen, M. H. Shaw, G. Redondo, and G. Nunez (2008)
Cancer Res. 68, 10060-10067
   Abstract »    Full Text »    PDF »
Mucosal Clearance of Capsule-Expressing Bacteria Requires Both TLR and Nucleotide-Binding Oligomerization Domain 1 Signaling.
T. A. Zola, E. S. Lysenko, and J. N. Weiser (2008)
J. Immunol. 181, 7909-7916
   Abstract »    Full Text »    PDF »
Nod2-Dependent Th2 Polarization of Antigen-Specific Immunity.
J. G. Magalhaes, J. H. Fritz, L. Le Bourhis, G. Sellge, L. H. Travassos, T. Selvanantham, S. E. Girardin, J. L. Gommerman, and D. J. Philpott (2008)
J. Immunol. 181, 7925-7935
   Abstract »    Full Text »    PDF »
Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction.
M. U. Gack, A. Kirchhofer, Y. C. Shin, K.-S. Inn, C. Liang, S. Cui, S. Myong, T. Ha, K.-P. Hopfner, and J. U. Jung (2008)
PNAS 105, 16743-16748
   Abstract »    Full Text »    PDF »
A polymer-type water-soluble peptidoglycan exhibited both Toll-like receptor 2- and NOD2-agonistic activities, resulting in synergistic activation of human monocytic cells.
M. Natsuka, A. Uehara, Shuhua Yang, S. Echigo, and H. Takada (2008)
Innate Immunity 14, 298-308
   Abstract »    PDF »
Cross-Tolerization between Nod1 and Nod2 Signaling Results in Reduced Refractoriness to Bacterial Infection in Nod2-Deficient Macrophages.
Y.-G. Kim, J.-H. Park, S. Daignault, K. Fukase, and G. Nunez (2008)
J. Immunol. 181, 4340-4346
   Abstract »    Full Text »    PDF »
A New Inflammatory Cytokine on the Block: Re-thinking Periodontal Disease and the Th1/Th2 Paradigm in the Context of Th17 Cells and IL-17.
S.L. Gaffen and G. Hajishengallis (2008)
Journal of Dental Research 87, 817-828
   Abstract »    Full Text »    PDF »
Nucleotide Oligomerization Domains 1 and 2: Regulation of Expression and Function in Preadipocytes.
T. Stroh, A. Batra, R. Glauben, I. Fedke, U. Erben, A. Kroesen, M. M. Heimesaat, S. Bereswill, S. Girardin, M. Zeitz, et al. (2008)
J. Immunol. 181, 3620-3627
   Abstract »    Full Text »    PDF »
Synergism between TLRs and NOD1/2 in Oral Epithelial Cells.
A. Uehara and H. Takada (2008)
Journal of Dental Research 87, 682-686
   Abstract »    Full Text »    PDF »
The Cytosolic Pattern Recognition Receptor NOD1 Induces Inflammatory Interleukin-8 during Chlamydia trachomatis Infection.
K. R. Buchholz and R. S. Stephens (2008)
Infect. Immun. 76, 3150-3155
   Abstract »    Full Text »    PDF »
Antibodies to Proteinase 3 Prime Human Oral, Lung, and Kidney Epithelial Cells To Secrete Proinflammatory Cytokines upon Stimulation with Agonists to Various Toll-Like Receptors, NOD1, and NOD2.
A. Uehara, Y. Hirabayashi, and H. Takada (2008)
Clin. Vaccine Immunol. 15, 1060-1066
   Abstract »    Full Text »    PDF »
Differential function of the NACHT-LRR (NLR) members Nod1 and Nod2 in arthritis.
L. A. B. Joosten, B. Heinhuis, S. Abdollahi-Roodsaz, G. Ferwerda, L. LeBourhis, D. J. Philpott, M.-A. Nahori, C. Popa, S. A. Morre, J. W. M. van der Meer, et al. (2008)
PNAS 105, 9017-9022
   Abstract »    Full Text »    PDF »
Inhibition of Nod2 Signaling and Target Gene Expression by Curcumin.
S. Huang, L. Zhao, K. Kim, D. S. Lee, and D. H. Hwang (2008)
Mol. Pharmacol. 74, 274-281
   Abstract »    Full Text »    PDF »
Mutations in ampG or ampD Affect Peptidoglycan Fragment Release from Neisseria gonorrhoeae.
D. L. Garcia and J. P. Dillard (2008)
J. Bacteriol. 190, 3799-3807
   Abstract »    Full Text »    PDF »
Human Langerhans cells selectively activated via Toll-like receptor 2 agonists acquire migratory and CD4+T cell stimulatory capacity.
M. Peiser, J. Koeck, C. J. Kirschning, B. Wittig, and R. Wanner (2008)
J. Leukoc. Biol. 83, 1118-1127
   Abstract »    Full Text »    PDF »
Lipoproteins Are Critical TLR2 Activating Toxins in Group B Streptococcal Sepsis.
P. Henneke, S. Dramsi, G. Mancuso, K. Chraibi, E. Pellegrini, C. Theilacker, J. Hubner, S. Santos-Sierra, G. Teti, D. T. Golenbock, et al. (2008)
J. Immunol. 180, 6149-6158
   Abstract »    Full Text »    PDF »
Pannexin-1-Mediated Intracellular Delivery of Muramyl Dipeptide Induces Caspase-1 Activation via Cryopyrin/NLRP3 Independently of Nod2.
N. Marina-Garcia, L. Franchi, Y.-G. Kim, D. Miller, C. McDonald, G.-J. Boons, and G. Nunez (2008)
J. Immunol. 180, 4050-4057
   Abstract »    Full Text »    PDF »
NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-{kappa}B and JNK pathways by inducing reactive oxygen species production.
I. Tattoli, L. A. Carneiro, M. Jehanno, J. G. Magalhaes, Y. Shu, D. J. Philpott, D. Arnoult, and S. E. Girardin (2008)
EMBO Rep. 9, 293-300
   Abstract »    Full Text »    PDF »
Lipoteichoic Acid Isolated from Lactobacillus plantarum Inhibits Lipopolysaccharide-Induced TNF-{alpha} Production in THP-1 Cells and Endotoxin Shock in Mice.
H. G. Kim, N.-R. Kim, M. G. Gim, J. M. Lee, S. Y. Lee, M. Y. Ko, J. Y. Kim, S. H. Han, and D. K. Chung (2008)
J. Immunol. 180, 2553-2561
   Abstract »    Full Text »    PDF »
LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 Expression in Human Lymphatic Endothelium.
Y. Sawa, T. Ueki, M. Hata, K. Iwasawa, E. Tsuruga, H. Kojima, H. Ishikawa, and S. Yoshida (2008)
Journal of Histochemistry & Cytochemistry 56, 97-109
   Abstract »    Full Text »    PDF »
A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-{kappa}B activation.
M. Hasegawa, Y. Fujimoto, P. C. Lucas, H. Nakano, K. Fukase, G. Nunez, and N. Inohara (2008)
EMBO J. 27, 373-383
   Abstract »    Full Text »    PDF »

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