title: Escherichia coli α-hemolysin counteracts the anti-virulence innate immune response triggered by the Rho GTPase activating toxin CNF1 during bacteremia.
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.
authors.affiliation: 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.
authors.forename: Mamady
authors.initials: M
authors.lastname: Diabate
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Munro
authors.affiliation: 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.
authors.forename: Elsa
authors.initials: E
authors.lastname: Garcia
authors.affiliation: Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France; INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Mort Cellulaire, Differentiation et Cancer, Nice, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jacquel
authors.affiliation: 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.
authors.forename: Gregory
authors.initials: G
authors.lastname: Michel
authors.affiliation: Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France; INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Mort Cellulaire, Differentiation et Cancer, Nice, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Obba
authors.affiliation: Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France; INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Mort Cellulaire, Differentiation et Cancer, Nice, France.
authors.forename: Diogo
authors.initials: D
authors.lastname: Goncalves
authors.affiliation: Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France; CNRS UMR7275, IPMC, Sophia Antipolis, France.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Luci
authors.affiliation: Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France; INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Mort Cellulaire, Differentiation et Cancer, Nice, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marchetti
authors.affiliation: Department of Medical Protein Research, VIB, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Demon
authors.affiliation: Aix-Marseille University UM 2, INSERM U 1104, CNRS UMR 7280, Marseille, France.
authors.forename: Clara
authors.initials: C
authors.lastname: Degos
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, CNRS UMR 6236, Faculté de Médecine, Marseille, France.
authors.forename: Yassina
authors.initials: Y
authors.lastname: Bechah
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, CNRS UMR 6236, Faculté de Médecine, Marseille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
authors.affiliation: Department of Medical Protein Research, VIB, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lamkanfi
authors.affiliation: Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France; INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Mort Cellulaire, Differentiation et Cancer, Nice, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Auberger
authors.affiliation: Aix-Marseille University UM 2, INSERM U 1104, CNRS UMR 7280, Marseille, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Washington, United States of America.
authors.forename: Lynda Maria
authors.initials: LM
authors.lastname: Stuart
authors.affiliation: 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.
authors.forename: Luce
authors.initials: L
authors.lastname: Landraud
authors.affiliation: 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.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
authors.affiliation: 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.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology*; D005260:Female; D006460:Hemolysin Proteins / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology*; D014774:Virulence; D037521:Virulence Factors / Q000276:immunology
chemical_list: D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli; D053583:Interleukin-1beta; D037521:Virulence Factors; C060296:cytotoxic necrotizing factor type 1