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

(2015) PLOS PATHOGENS. 11(3).
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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-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.
Keywords
PATHOGENS, CASPASE-1, INFLAMMASOME, BACTERIAL, E.-COLI, BLADDER INFECTION, PROTEASOMAL DEGRADATION, INTERLEUKIN-1-BETA CONVERTING-ENZYME, PROTEIN, SYSTEM

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Chicago
Diabate, Mamady, Patrick Munro, Elsa Garcia, Arnaud Jacquel, Gregory Michel, Sandrine Obba, Diogo Goncalves, et al. 2015. “Escherichia Coli Α-hemolysin Counteracts the Anti-virulence Innate Immune Response Triggered by the Rho GTPase Activating Toxin CNF1 During Bacteremia.” Plos Pathogens 11 (3).
APA
Diabate, M., Munro, P., Garcia, E., Jacquel, A., Michel, G., Obba, S., Goncalves, D., et al. (2015). Escherichia coli α-hemolysin counteracts the anti-virulence innate immune response triggered by the Rho GTPase activating toxin CNF1 during bacteremia. PLOS PATHOGENS, 11(3).
Vancouver
1.
Diabate M, Munro P, Garcia E, Jacquel A, Michel G, Obba S, 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(3).
MLA
Diabate, Mamady, Patrick Munro, Elsa Garcia, 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 11.3 (2015): n. pag. Print.
@article{6895913,
  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-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.},
  articleno    = {e1004732},
  author       = {Diabate, Mamady and Munro, Patrick and Garcia, Elsa and Jacquel, Arnaud and Michel, Gregory and Obba, Sandrine and Goncalves, Diogo and Luci, Carmelo and Marchetti, Sandrine and Demon, Dieter and Degos, Clara and Bechah, Yassina and Mege, Jean-Louis and Lamkanfi, Mohamed and Auberger, Patrick and Gorvel, Jean-Pierre and Stuart, Lynda Maria and Landraud, Luce and Lemichez, Emmanuel and Boyer, Laurent},
  issn         = {1553-7366},
  journal      = {PLOS PATHOGENS},
  keyword      = {PATHOGENS,CASPASE-1,INFLAMMASOME,BACTERIAL,E.-COLI,BLADDER INFECTION,PROTEASOMAL DEGRADATION,INTERLEUKIN-1-BETA CONVERTING-ENZYME,PROTEIN,SYSTEM},
  language     = {eng},
  number       = {3},
  pages        = {20},
  title        = {Escherichia coli \ensuremath{\alpha}-hemolysin counteracts the anti-virulence innate immune response triggered by the Rho GTPase activating toxin CNF1 during bacteremia},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1004732},
  volume       = {11},
  year         = {2015},
}

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