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

PLoS Pathogens

Lynda Maria Stuart²  Laurent Boyer³  Emmanuel Lemichez⁴  Sandrine Marchetti⁴  Jean-Louis Mege⁴  Patrick Auberger⁴  Sandrine Obba⁵  Mamady Diabate⁵  Dieter Demon⁵  Arnaud Jacquel⁵  Elsa Garcia⁶  Patrick Munro⁷  Carmelo Luci⁷  Gregory Michel⁷  Diogo Goncalves⁷  Luce Landraud⁷  Yassina Bechah⁷  Mohamed Lamkanfi⁷  Jean-Pierre Gorvel⁷  Clara Degos⁷ 

[1] Department of Biochemistry, Ghent University, Ghent, Belgium;CNRS UMR7275, IPMC, Sophia Antipolis, France;Department of Medical Protein Research, VIB, Ghent, Belgium;INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Mort Cellulaire, Differentiation et Cancer, Nice, France;INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Toxines Microbiennes dans la relation hôte pathogènes, Nice, France;Laboratoire de Bactériologie, CHU de Nice, Hôpital l’Archet, Nice, France;Université de Nice-Sophia-Antipolis, UFR Médecine, Nice, France

关键词: Toxins;    Blood;    Escherichia coli infections;    Monocytes;    Bacteremia;    Immune response;    Bacterial pathogens;    Inflammation;   

DOI  :  10.1371/journal.ppat.1004732

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY