Published March 2015
| Version v1
Journal article
Escherichia coli α-Hemolysin Counteracts the Anti-Virulence Innate Immune Response Triggered by the Rho GTPase Activating Toxin CNF1 during Bacteremia
Creators
- Diabate, Mamady
- Munro, Patrick
- Garcia, Elsa
- Jacquel, Arnaud
- Michel, Gregory
- Obba, Sandrine
- Goncalves, Diogo
- Luci, Carmelo
- Marchetti, Sandrine
- Demon, Dieter
- Degos, Clara
- Bechah, Yassina
- Mege, Jean-Louis
- Lamkanfi, Mohamed
- Auberger, Patrick
- Gorvel, Jean-Pierre
- Stuart, Lynda Maria
- Landraud, Luce
- Lemichez, Emmanuel
- Boyer, Laurent
Contributors
Others:
- Centre méditerranéen de médecine moléculaire (C3M) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)
- Laboratoire de Bactériologie ; CHU de Nice
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Department of Medical Protein Research ; Universiteit Gent = Ghent University (UGENT)
- Centre d'Immunologie de Marseille - Luminy (CIML) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE) ; Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48 ; Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)
- Benaroya Research Institute at Virginia Mason ; Benaroya Research Institute at Virginia Mason
- Laboratoire de Bactériologie ; Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet
Description
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-1 beta 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-1 beta antagonist. In vitro experiments further revealed the synergistic effects of CNF1 and LPS in promoting the maturation/secretion of IL-1 beta and establishing the roles of Rac, ASC and caspase-1 in this pathway. Furthermore, we found that the Phi-hemolysin toxin inhibits IL-1 beta 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.
Abstract
International audienceAdditional details
Identifiers
- URL
- https://hal-amu.archives-ouvertes.fr/hal-01219225
- URN
- urn:oai:HAL:hal-01219225v1