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

PLoS Pathogens
Mamady DiabateLaurent Boyer

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.

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Citations

Dec 8, 2015·Nature Reviews. Microbiology·Matteo Dal Peraro, F Gisou van der Goot
Mar 26, 2016·Frontiers in Immunology·Julie Guignot, Guy Tran Van Nhieu
May 9, 2018·International Journal of Molecular Sciences·Laura Gall-MasThorbjørn Krejsgaard
Oct 25, 2017·Biotechnology Progress·Andrea ColarussoMaria Luisa Tutino
Mar 15, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ambika M V MurthyMatthew J Sweet
Nov 9, 2017·Molecular Microbiology·Patrick J Woida, Karla J F Satchell
Nov 11, 2016·Veterinary Research·Sofia HenriquesLuisa Mateus
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Harvey TawfikJean-Baptiste Fleury
Apr 30, 2021·PLoS Pathogens·Océane Dufies, Laurent Boyer

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Methods Mentioned

BETA
GTPases
GTPase
ELISArray
ELISA
co-immunoprecipitation
transfection
Flow cytometry
PCR
FCS
ICE

Software Mentioned

GraphPad
Prism

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