Open AccessEscherichia coli α-Hemolysin Counteracts the Anti-Virulence Innate Immune Response Triggered by the Rho GTPase Activating Toxin CNF1 during Bacteremia
Author(s) -
Mamady Diabate,
Patrick Munro,
E. Garcia,
Arnaud Jacquel,
Grégory Michel,
Sandrine Obba,
Diogo Nunes Gonçalves,
Carmelo Luci,
Sandrine Marchetti,
Dieter Demon,
Clara Degos,
Yassina Bechah,
JeanLouis Mège,
Mohamed Lamkanfi,
Patrick Auberger,
JeanPierre Gorvel,
Lynda M. Stuart,
Luce Landraud,
Emmanuel Lemichez,
Laurent Boyer
Publication year - 2015
Publication title -
hal (le centre pour la communication scientifique directe)
Language(s) - English
DOI - 10.1371/journal.ppat.1004732.s007
Subject(s) - virulence , hemolysin , microbiology and biotechnology , innate immune system , escherichia coli , toxin , immune system , bacteremia , biology , gtpase , immunology , gene , antibiotics , genetics
International audienceThe 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