title: Subversion of human intestinal mucosa innate immunity by a Crohn's disease-associated E. coli.
abstract: Adherent-invasive Escherichia coli (AIEC), associated with Crohn's disease, are likely candidate contributory factors in the disease. However, signaling pathways involved in human intestinal mucosa innate host response to AIEC remain unknown. Here we use a 3D model of human intestinal mucosa explant culture to explore the effects of the AIEC strain LF82 on two innate immunity platforms, i.e., the inflammasome through evaluation of caspase-1 status, and NFκB signaling. We showed that LF82 bacteria enter and survive within a few intestinal epithelial cells and macrophages, without altering the mucosa overall architecture. Although 4-h infection with a Salmonella strain caused crypt disorganization, caspase-1 activation, and mature IL-18 production, LF82 bacteria were unable to activate caspase-1 and induce IL-18 production. In parallel, LF82 bacteria activated NFκB signaling in epithelial cells through IκBα phosphorylation, NFκBp65 nuclear translocation, and TNFα secretion. In addition, NFκB activation was crucial for the maintenance of epithelial homeostasis upon LF82 infection. In conclusion, here we decipher at the whole-mucosa level the mechanisms of the LF82-induced subversion of innate immunity that, by maintaining host cell integrity, ensure intracellular bacteria survival.
authors.affiliation: EA 4273 Biometadys, Université de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Jarry
authors.affiliation: 1] UPRES EA3826 Université de Nantes, Faculté de Médecine, Nantes, France [2] CHU Nantes, Service de Bactériologie-Hygiène, Nantes, France.
authors.forename: L
authors.initials: L
authors.lastname: Crémet
authors.affiliation: 1] UPRES EA3826 Université de Nantes, Faculté de Médecine, Nantes, France [2] CHU Nantes, Service de Bactériologie-Hygiène, Nantes, France.
authors.forename: N
authors.initials: N
authors.lastname: Caroff
authors.affiliation: EA 4273 Biometadys, Université de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Bou-Hanna
authors.affiliation: CHU Nantes, Service d'Anatomie et Cytologie Pathologiques, Nantes, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Mussini
authors.affiliation: 1] UPRES EA3826 Université de Nantes, Faculté de Médecine, Nantes, France [2] CHU Nantes, Service de Bactériologie-Hygiène, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Reynaud
authors.affiliation: CNRS UMR8076, Université Paris-Sud, Faculté de Pharmacie, Chatenay-Malabry, France.
authors.forename: A L
authors.initials: AL
authors.lastname: Servin
authors.affiliation: 1] EA 4273 Biometadys, Université de Nantes, Faculté de Médecine, Nantes, France [2] CHU Nantes, Service d'Anatomie et Cytologie Pathologiques, Nantes, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Mosnier
authors.affiliation: CNRS UMR8076, Université Paris-Sud, Faculté de Pharmacie, Chatenay-Malabry, France.
authors.forename: V
authors.initials: V
authors.lastname: Liévin-Le Moal
authors.affiliation: 1] EA 4273 Biometadys, Université de Nantes, Faculté de Médecine, Nantes, France [2] CHU Nantes, Service d'Anatomie et Cytologie Pathologiques, Nantes, France.
authors.forename: C L
authors.initials: CL
authors.lastname: Laboisse
mesh_terms: D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000276:immunology; D057131:Immune Evasion; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D058847:Inflammasomes / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D012475:Salmonella / Q000276:immunology*; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D020672:I-kappa B Proteins; C000589760:IL18 protein, human; D058847:Inflammasomes; D020382:Interleukin-18; C000606204:NFKBIA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D020170:Caspase 1