Escherichia coli α-Hemolysin Counteracts the Anti-Virulence Innate Immune Response Triggered by the Rho GTPase Activating Toxin CNF1 during Bacteremia

Mamady Diabate (1, 2) , Patrick Munro (1) , Elsa Garcia (1) , Arnaud Jacquel (1) , Gregory Michel (1) , Sandrine Obba (1) , Diogo Goncalves (1) , Carmelo Luci (3) , Sandrine Marchetti (1) , Dieter Demon (4) , Clara Degos (5) , Yassina Bechah (6) , Jean-Louis Mege (6) , Mohamed Lamkanfi (4) , Patrick Auberger (1) , Jean-Pierre Gorvel (5) , Lynda Maria Stuart (7) , Luce Landraud (1, 8) , Emmanuel Lemichez (1) , Laurent Boyer (1)

1 C3M - Centre méditerranéen de médecine moléculaire
2 Laboratoire de Bactériologie
3 IPMC - Institut de pharmacologie moléculaire et cellulaire
4 Department of Medical Protein Research
5 CIML - Centre d'Immunologie de Marseille - Luminy
6 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
7 BRI - Benaroya Research Institute [Seattle]
8 Laboratoire de Bactériologie

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.

Mots clés: INTERLEUKIN-1-BETA CONVERTING-ENZYME; PROTEASOMAL DEGRADATION; BLADDER INFECTION; E.-COLI; BACTERIAL; INFLAMMASOME; PATHOGENS; CASPASE-1; PROTEIN; SYSTEM

Domaines: Médecine humaine et pathologie

Mamady Diabate, Patrick Munro, Elsa Garcia, Arnaud Jacquel, Gregory Michel, et al.. Escherichia coli α-Hemolysin Counteracts the Anti-Virulence Innate Immune Response Triggered by the Rho GTPase Activating Toxin CNF1 during Bacteremia. PLoS Pathogens, 2015, 11 (UNSP e1004732), ⟨10.1371/journal.ppat.1004732.s007⟩. ⟨hal-01219225⟩