Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome

Authors

  • Sarah Kim,

    1. Institute for Clinical Chemistry and Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, Bonn, Germany
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  • Franz Bauernfeind,

    1. Institute for Clinical Chemistry and Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, Bonn, Germany
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  • Andrea Ablasser,

    1. Institute for Clinical Chemistry and Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, Bonn, Germany
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  • Gunther Hartmann,

    1. Institute for Clinical Chemistry and Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, Bonn, Germany
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  • Katherine A. Fitzgerald,

    1. Division of Infectious Diseases & Immunology, University of Massachusetts Medical School, Worcester, MA, USA
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  • Eicke Latz,

    1. Institute of Innate Immunology, University Hospital, University of Bonn, Bonn, Germany
    2. Division of Infectious Diseases & Immunology, University of Massachusetts Medical School, Worcester, MA, USA
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  • Veit Hornung

    Corresponding author
    1. Institute for Clinical Chemistry and Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, Bonn, Germany
    • Institute for Clinical Chemistry and Pharmacology, University Hospital, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany Fax: +49-228-287-51201
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Abstract

The inflammasome pathway functions to regulate caspase-1 activation in response to a broad range of stimuli. Caspase-1 activation is required for the maturation of the pivotal pro-inflammatory cytokines of the pro-IL-1β family. In addition, caspase-1 activation leads to a certain type of cell death known as pyroptosis. Activation of the inflammasome has been shown to play a critical role in the recognition and containment of various microbial pathogens, including the intracellularly replicating Listeria monocytogenes; however, the inflammasome pathways activated during L. monocytogenes infection are only poorly defined. Here, we demonstrate that L. monocytogenes activates both the NLRP3 and the AIM2 inflammasome, with a predominant involvement of the AIM2 inflammasome. In addition, L. monocytogenes-triggered cell death was diminished in the absence of both AIM2 and NLRP3, and is concomitant with increased intracellular replication of L. monocytogenes. Altogether, these data establish a role for DNA sensing through the AIM2 inflammasome in the detection of intracellularly replicating bacteria.

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