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Nod2 Is a General Sensor of Peptidoglycan through Muramyl Dipeptide (MDP) Detection*

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Nod2 activates the NF-κB pathway following intracellular stimulation by bacterial products. Recently, mutations inNod2 have been shown to be associated with Crohn's disease, suggesting a role for bacteria-host interactions in the etiology of this disorder. We show here that Nod2 is a general sensor of peptidoglycan through the recognition of muramyl dipeptide (MDP), the minimal bioactive peptidoglycan motif common to all bacteria. Moreover, the 3020insC frameshift mutation, the most frequent Nod2 variant associated with Crohn's disease patients, fully abrogates Nod2-dependent detection of peptidoglycan and MDP. Together, these results impact on the understanding of Crohn's disease development. Additionally, the characterization of Nod2 as the first pathogen-recognition molecule that detects MDP will help to unravel the well known biological activities of this immunomodulatory compound.

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Published, JBC Papers in Press, January 13, 2003, DOI 10.1074/jbc.C200651200

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This work was supported in part by a grant from the Institut Pasteur, “Program Transversal de Recherche” (to S. E. G. and D. J. P.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Supported by a grant from Danone Vitapole, Paris, France.

Supported by a postdoctoral fellowship from the Fundação para a Ciência e a Tecnologia, Portugal (SFRH/BPD/1567/2000).

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Supported by a grant from the Ministère Français de l'Education Nationale.

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These authors share senior authorship.

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Howard Hughes International Research Scholar.