title: Hyperinvasive Meningococci Induce Intra-nuclear Cleavage of the NF-κB Protein p65/RelA by Meningococcal IgA Protease.
abstract: Differential modulation of NF-κB during meningococcal infection is critical in innate immune response to meningococcal disease. Non-invasive isolates of Neisseria meningitidis provoke a sustained NF-κB activation in epithelial cells. However, the hyperinvasive isolates of the ST-11 clonal complex (ST-11) only induce an early NF-κB activation followed by a sustained activation of JNK and apoptosis. We show that this temporal activation of NF-κB was caused by specific cleavage at the C-terminal region of NF-κB p65/RelA component within the nucleus of infected cells. This cleavage was mediated by the secreted 150 kDa meningococcal ST-11 IgA protease carrying nuclear localisation signals (NLS) in its α-peptide moiety that allowed efficient intra-nuclear transport. In a collection of non-ST-11 healthy carriage isolates lacking NLS in the α-peptide, secreted IgA protease was devoid of intra-nuclear transport. This part of iga polymorphism allows non-invasive isolates lacking NLS, unlike hyperinvasive ST-11 isolates of N. meningitides habouring NLS in their α-peptide, to be carried asymptomatically in the human nasopharynx through selective eradication of their ability to induce apoptosis in infected epithelial cells.
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France.
authors.forename: Anissa
authors.initials: A
authors.lastname: Besbes
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France.
authors.forename: Salomé
authors.initials: S
authors.lastname: Le Goff
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Antunes
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Terrade
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Hong
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France.
authors.forename: Dario
authors.initials: D
authors.lastname: Giorgini
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France.
authors.forename: Muhamed-Kheir
authors.initials: MK
authors.lastname: Taha
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France.
authors.forename: Ala-Eddine
authors.initials: AE
authors.lastname: Deghmane
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D017209:Apoptosis / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008589:Meningococcal Infections / Q000276:immunology / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009345:Neisseria meningitidis / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D019913:Nuclear Localization Signals; D060888:Real-Time Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014162:Transfection
chemical_list: D001426:Bacterial Proteins; D019913:Nuclear Localization Signals; D051996:Transcription Factor RelA; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase