title: Correlation between cytotoxicity induced by Pseudomonas aeruginosa clinical isolates from acute infections and IL-1β secretion in a model of human THP-1 monocytes.
abstract: Type III secretion system (T3SS) in Pseudomonas aeruginosa is associated with poor clinical outcome in acute infections. T3SS allows for injection of bacterial exotoxins (e.g. ExoU or ExoS) into the host cell, causing cytotoxicity. It also activates the cytosolic NLRC4 inflammasome, activating caspase-1, inducing cytotoxicity and release of mature IL-1β, which impairs bacterial clearance. In addition, flagellum-mediated motility has been suggested to also modulate inflammasome response and IL-1β release. Yet the capacity of clinical isolates to induce IL-1β release and its relation with cytotoxicity have never been investigated. Using 20 clinical isolates from acute infections with variable T3SS expression levels and human monocytes, our aim was to correlate IL-1β release with toxin expression, flagellar motility and cytotoxicity. ExoU-producing isolates caused massive cell death but minimal release of IL-1β, while those expressing T3SS but not ExoU (i.e. expressing ExoS or no toxins) induced caspase-1 activation and IL-1β release, the level of which was correlated with cytotoxicity. Both effects were prevented by a specific caspase-1 inhibitor. Flagellar motility was not correlated with cytotoxicity or IL-1β release. No apoptosis was detected. Thus, T3SS cytotoxicity is accompanied by a modification in cytokine balance for P. aeruginosa clinical isolates that do not express ExoU.
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Ahalieyah
authors.initials: A
authors.lastname: Anantharajah
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Julien M
authors.initials: JM
authors.lastname: Buyck
authors.affiliation: Host-Pathogen Translational Research Group, Université Droit et Santé de Lille, Faculté de Médecine, CHRU Lille, 59000 Lille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Faure
authors.affiliation: Centre National de Référence de la résistance chez Pseudomonas aeruginosa, CHU Dinant-Godinne UCL Namur, Université catholique de Louvain, 5530 Yvoir, Belgium.
authors.forename: Youri
authors.initials: Y
authors.lastname: Glupczynski
authors.affiliation: Laboratoire de microbiologie, Cliniques universitaires Saint Luc, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Hector
authors.initials: H
authors.lastname: Rodriguez-Villalobos
authors.affiliation: Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, 1120 Neder-over-Heembeek, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: De Vos
authors.affiliation: Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, 1120 Neder-over-Heembeek, Belgium.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pirnay
authors.affiliation: Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, 1120 Neder-over-Heembeek, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Bilocq
authors.affiliation: Host-Pathogen Translational Research Group, Université Droit et Santé de Lille, Faculté de Médecine, CHRU Lille, 59000 Lille, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Guery
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Mingeot-Leclercq
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium francoise.vanbambeke@uclouvain.be.
authors.forename: Françoise
authors.initials: F
authors.lastname: Van Bambeke
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005407:Flagella / Q000502:physiology*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008124:Locomotion; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology* / Q000502:physiology*; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology
chemical_list: D001427:Bacterial Toxins; D053583:Interleukin-1beta
keywords: ExoS; ExoU; TNF-alpha; flagellin; inflammasome; type three secretion system