title: Late repression of NF-κB activity by invasive but not non-invasive meningococcal isolates is required to display apoptosis of epithelial cells.
abstract: Meningococcal invasive isolates of the ST-11 clonal complex are most frequently associated with disease and rarely found in carriers. Unlike carriage isolates, invasive isolates induce apoptosis in epithelial cells through the TNF-α signaling pathway. While invasive and non-invasive isolates are both able to trigger the TLR4/MyD88 pathway in lipooligosaccharide (LOS)-dependant manner, we show that only non-invasive isolates were able to induce sustained NF-κB activity in infected epithelial cells. ST-11 invasive isolates initially triggered a strong NF-κB activity in infected epithelial cells that was abolished after 9 h of infection and was associated with sustained activation of JNK, increased levels of membrane TNFR1, and induction of apoptosis. In contrast, infection with carriage isolates lead to prolonged activation of NF-κB that was associated with a transient activation of JNK increased TACE/ADAM17-mediated shedding of TNFR1 and protection against apoptosis. Our data provide insights to understand the meningococcal duality between invasiveness and asymptomatic carriage.
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France. ala-eddine.deghmane@pasteur.fr
authors.forename: Ala-Eddine
authors.initials: AE
authors.lastname: Deghmane
authors.forename: Hela
authors.initials: H
authors.lastname: El Kafsi
authors.forename: Dario
authors.initials: D
authors.lastname: Giorgini
authors.forename: Aziza
authors.initials: A
authors.lastname: Abaza
authors.forename: Muhamed-Kheir
authors.initials: MK
authors.lastname: Taha
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D017209:Apoptosis; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008589:Meningococcal Infections / Q000378:metabolism* / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D048670:MAP Kinase Kinase 4; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human