title: Nod1 participates in the innate immune response to Pseudomonas aeruginosa.
abstract: The mammalian innate immune system recognizes pathogen-associated molecular patterns through pathogen recognition receptors. Nod1 has been described recently as a cytosolic receptor that detects specifically diaminopimelate-containing muropeptides from Gram-negative bacteria peptidoglycan. In the present study we investigated the potential role of Nod1 in the innate immune response against the opportunistic pathogen Pseudomonas aeruginosa. We demonstrate that Nod1 detects the P. aeruginosa peptidoglycan leading to NF-kappaB activation and that this activity is diminished in epithelial cells expressing a dominant-negative Nod1 construct or in mouse embryonic fibroblasts from Nod1 knock-out mice infected with P. aeruginosa. Finally, we demonstrate that the cytokine secretion kinetics and bacterial killing are altered in Nod1-deficient cells infected with P. aeruginosa in the early stages of infection.
authors.affiliation: Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ Cep. 21.941 590, Brazil. lhtravassos@ufrj.br
authors.forename: Leonardo H
authors.initials: LH
authors.lastname: Travassos
authors.forename: Leticia A M
authors.initials: LA
authors.lastname: Carneiro
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Boneca
authors.forename: Ramon
authors.initials: R
authors.lastname: Lemos
authors.forename: Marcelo T
authors.initials: MT
authors.lastname: Bozza
authors.forename: Regina C P
authors.initials: RC
authors.lastname: Domingues
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: John
authors.initials: J
authors.lastname: Bertin
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Plotkowski
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005799:Genes, Dominant; D006801:Humans; D007113:Immunity, Innate; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout / Q000382:microbiology; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein; D010457:Peptidoglycan / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D010457:Peptidoglycan