title: Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2.
abstract: 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.
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, INSERM U389, Institut Pasteur, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France. girardin@pasteur.fr
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
authors.forename: Leonardo H
authors.initials: LH
authors.lastname: Travassos
authors.forename: Mireille
authors.initials: M
authors.lastname: Hervé
authors.forename: Didier
authors.initials: D
authors.lastname: Blanot
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Boneca
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.forename: Dominique
authors.initials: D
authors.lastname: Mengin-Lecreulx
mesh_terms: D000117:Acetylglucosamine; D048868:Adaptor Proteins, Signal Transducing; D001424:Bacterial Infections / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009112:Muramic Acids; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D010446:Peptide Fragments / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology*; D013379:Substrate Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009112:Muramic Acids; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D010446:Peptide Fragments; D010457:Peptidoglycan; C031651:N-acetylmuramic acid; D000117:Acetylglucosamine