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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.

Original publication

DOI

10.1371/journal.ppat.1004732

Type

Journal article

Journal

PLoS Pathog

Publication Date

03/2015

Volume

11

Keywords

Animals, Bacteremia, Bacterial Toxins, Disease Models, Animal, Escherichia coli, Escherichia coli Infections, Escherichia coli Proteins, Female, Hemolysin Proteins, Host-Pathogen Interactions, Immunity, Innate, Interleukin-1beta, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction, Virulence, Virulence Factors