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Pathog Dis. 2015 Oct;73(7). pii: ftv049. doi: 10.1093/femspd/ftv049. Epub 2015 Jul 22.

Correlation between cytotoxicity induced by Pseudomonas aeruginosa clinical isolates from acute infections and IL-1β secretion in a model of human THP-1 monocytes.

Author information

1
Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
2
Host-Pathogen Translational Research Group, Université Droit et Santé de Lille, Faculté de Médecine, CHRU Lille, 59000 Lille, France.
3
Centre National de Référence de la résistance chez Pseudomonas aeruginosa, CHU Dinant-Godinne UCL Namur, Université catholique de Louvain, 5530 Yvoir, Belgium.
4
Laboratoire de microbiologie, Cliniques universitaires Saint Luc, Université catholique de Louvain, 1200 Brussels, Belgium.
5
Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, 1120 Neder-over-Heembeek, Belgium.
6
Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium francoise.vanbambeke@uclouvain.be.

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.

KEYWORDS:

ExoS; ExoU; TNF-alpha; flagellin; inflammasome; type three secretion system

PMID:
26203053
PMCID:
PMC4626600
DOI:
10.1093/femspd/ftv049
[Indexed for MEDLINE]
Free PMC Article

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