Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; Carrier Proteins; Immunoblotting; Listeria monocytogenes; Listeriosis; Macrophages; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Nuclear Proteins
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-1beta 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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Citation: Eur J Immunol. 2010 Jun;40(6):1545-51. Link to article on publisher's site