1. 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

Anantharajah A(1), Buyck JM(1), Faure E(2), Glupczynski Y(3),
Rodriguez-Villalobos H(4), De Vos D(5), Pirnay JP(5), Bilocq F(5), Guery B(2),
Tulkens PM(1), Mingeot-Leclercq MP(1), Van Bambeke F(6).

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.

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.

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PMCID: PMC4626600 [Available on 2016-10-01]
PMID: 26203053  [PubMed - in process]