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PLoS Pathog. 2015 Mar 17;11(3):e1004732. doi: 10.1371/journal.ppat.1004732. eCollection 2015 Mar.

Escherichia coli α-hemolysin counteracts the anti-virulence innate immune response triggered by the Rho GTPase activating toxin CNF1 during bacteremia.

Author information

1
INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Toxines Microbiennes dans la relation hôte pathogènes, Nice, France; Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France; Laboratoire de Bactériologie, CHU de Nice, Hôpital l'Archet, Nice, France.
2
INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Toxines Microbiennes dans la relation hôte pathogènes, Nice, France; Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France.
3
Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France; INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Mort Cellulaire, Differentiation et Cancer, Nice, France.
4
Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France; CNRS UMR7275, IPMC, Sophia Antipolis, France.
5
Department of Medical Protein Research, VIB, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium.
6
Aix-Marseille University UM 2, INSERM U 1104, CNRS UMR 7280, Marseille, France.
7
Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, CNRS UMR 6236, Faculté de Médecine, Marseille, France.
8
Benaroya Research Institute at Virginia Mason, Seattle, Washington, United States of America.

Abstract

The detection of the activities of pathogen-encoded virulence factors by the innate immune system has emerged as a new paradigm of pathogen recognition. Much remains to be determined with regard to the molecular and cellular components contributing to this defense mechanism in mammals and importance during infection. Here, we reveal the central role of the IL-1β signaling axis and Gr1+ cells in controlling the Escherichia coli burden in the blood in response to the sensing of the Rho GTPase-activating toxin CNF1. Consistently, this innate immune response is abrogated in caspase-1/11-impaired mice or following the treatment of infected mice with an IL-1β antagonist. In vitro experiments further revealed the synergistic effects of CNF1 and LPS in promoting the maturation/secretion of IL-1β and establishing the roles of Rac, ASC and caspase-1 in this pathway. Furthermore, we found that the α-hemolysin toxin inhibits IL-1β secretion without affecting the recruitment of Gr1+ cells. Here, we report the first example of anti-virulence-triggered immunity counteracted by a pore-forming toxin during bacteremia.

PMID:
25781937
PMCID:
PMC4363529
DOI:
10.1371/journal.ppat.1004732
[Indexed for MEDLINE]
Free PMC Article

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