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J. Biol. Chem., Vol. 278, Issue 43, 41702-41708, October 24, 2003
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¶¶
From the
Unité de Pathogénie Microbienne Moléculaire, INSERM U389, ¶Groupe d'Immunité Innée et Signalisation, and Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, 28, Rue du Dr. Roux, 75724 Paris Cedex 15, France and **Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, Unité Mixte de Recherche 8619 CNRS, Université Paris-Sud, Bât. 430, 91405 Orsay, France
Nod1 and Nod2 are mammalian proteins implicated in the intracellular detection of pathogen-associated molecular patterns. Recently, naturally occurring peptidoglycan (PG) fragments were identified as the microbial motifs sensed by Nod1 and Nod2. Whereas Nod2 detects GlcNAc-MurNAc dipeptide (GM-Di), Nod1 senses a unique diaminopimelate-containing GlcNAc-MurNAc tripeptide muropeptide (GM-TriDAP) found mostly in Gram-negative bacterial PGs. Because Nod1 and Nod2 detect similar yet distinct muropeptides, we further analyzed the molecular sensing specificity of Nod1 and Nod2 toward PG fragments. Using a wide array of natural or modified muramyl peptides, we show here that Nod1 and Nod2 have evolved divergent strategies to achieve PG sensing. By defining the PG structural requirements for Nod1 and Nod2 sensing, this study reveals how PG processing and modifications, either by host or bacterial enzymes, may affect innate immune responses.
Received for publication, July 5, 2003
* This work was supported in part by a grant from the Institut Pasteur "Programme Transversal de Recherche" (to S. E. G. and D. J. P.) and CNRS Grant UMR 8619. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|| Supported by a studentship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/Ministério de Educação (CAPES/MEC), Brazil.
Supported by a post-doctoral fellowship from the Fundação para a Ciência e a Tecnologia, Portugal.
¶¶ Howard Hughes International Research Scholar.
Supported by a grant from Danone Vitapole, Paris, France, and to whom correspondence should be addressed. Tel.: 33-1-40-61-37-71; Fax: 33-1-45-68-89-53; E-mail: girardin{at}pasteur.fr.
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