Listeria monocytogenes is sensed by the NLRP3 and AIM2 Inflammasome

Institute for Clinical Chemistry and Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, Bonn, Germany.
European Journal of Immunology (Impact Factor: 4.03). 06/2010; 40(6):1545-51. DOI: 10.1002/eji.201040425
Source: PubMed


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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Available from: Eicke Latz, Mar 15, 2014
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    • "Bacteria Listeria monocytogenes, Staphylococcus aureus, Vibrio cholera, Neisseria gonorrhoeae ROS or not yet determined Duncan et al. (2009), Khare et al. (2012), Kim et al. (2010), Mariathasan et al. (2006), Warren et al. (2008), Wu et al. (2010) Fungi Candida albicans, Saccharomyces cerevisiae (72) Not yet determined Gross et al. (2009) Virus Sendai virus, Influenza Adenovirus, MCMV ROS or not yet determined Allen et al. (2009), Ito et al. (2012), Kanneganti et al. (2006) Protozoa Plasmodium malariae Not yet determined Dostert et al. (2009), Shio et al. (2009) through release of cytokines, nitric oxide, and other ROS, which may adversely impact adjacent neurons. These data suggest that ␣synuclein can act as a DAMP activating microglial PRRs and inciting oxidative stress (Béraud et al., 2011). "
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    ABSTRACT: Accumulating evidence indicates that aging is associated with a chronic low-level inflammation, termed sterile-inflammation. Sterile-inflammation is a form of pathogen-free inflammation caused by mechanical trauma, ischemia, stress or environmental conditions such as ultra-violet radiation. These damage-related stimuli induce the secretion of molecular agents collectively termed danger-associated molecular patterns (DAMPs). DAMPs are recognized by virtue of specialized innate immune receptors, such as toll-like receptors (TLRs) and NOD-like receptor family, pyrin domain containing 3 (NLRP3). These receptors initiate signal transduction pathways, which typically drive inflammation in response to microbe-associated molecular patterns (MAMPs) and/or DAMPs. This review summarizes the current knowledge on DAMPs-mediated sterile-inflammation, its associated downstream signaling, and discusses the possibility that DAMPs activating TLRs or NLRP3 complex mediate sterile inflammation during aging and in aging-related pathologies. Copyright © 2015. Published by Elsevier B.V.
    Ageing Research Reviews 01/2015; DOI:10.1016/j.arr.2015.01.003 · 4.94 Impact Factor
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    • "The importance of inflammasome activation in mediating bacterial control is also highlighted by inflammasome-evasion strategies employed by several pathogens. This is nicely demonstrated by the food-borne pathogen L. monocytogenes; in vitro, L. monocytogenes induces inflammasome responses via NLRP3 through listeriolysin (Warren et al. 2008; Meixenberger et al. 2010; Wu et al. 2010), via NLRC4 through flagellin (Warren et al. 2008), and via AIM2 and RIG-I through released DNA (Kim et al. 2010; Sauer et al. 2010; Tsuchiya et al. 2010; Wu et al. 2010; Abdullah et al. 2012). However, DNA release is kept at a minimum in wild-type bacteria, and flagellin is strongly down-regulated during murine infection (Sauer et al. 2010, 2011). "
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    ABSTRACT: Inflammasomes are large cytosolic multiprotein complexes that assemble in response to detection of infection- or stress-associated stimuli and lead to the activation of caspase-1-mediated inflammatory responses, including cleavage and unconventional secretion of the leaderless proinflammatory cytokines IL-1β and IL-18, and initiation of an inflammatory form of cell death referred to as pyroptosis. Inflammasome activation can be induced by a wide variety of microbial pathogens and generally mediates host defense through activation of rapid inflammatory responses and restriction of pathogen replication. In addition to its role in defense against pathogens, recent studies have suggested that the inflammasome is also a critical regulator of the commensal microbiota in the intestine. Finally, inflammasomes have been widely implicated in the development and progression of various chronic diseases, such as gout, atherosclerosis, and metabolic syndrome. In this perspective, we discuss the role of inflammasomes in infectious and noninfectious inflammation and highlight areas of interest for future studies of inflammasomes in host defense and chronic disease.
    Cold Spring Harbor perspectives in biology 10/2014; 6(12). DOI:10.1101/cshperspect.a016287 · 8.68 Impact Factor
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    • "The NLRC4 inflammasome is activated in response to cytosolic flagellin from various gram-negative bacteria or components of the bacterial type three or four secretion systems (Mariathasan et al., 2004; Franchi et al., 2006; Miao et al., 2006; Zamboni et al., 2006; Suzuki et al., 2007; Miao et al., 2008; Chen and Nunez, 2011). Cytosolic double-stranded DNA from pathogens such as Franscisella tularensis and Listeria monocytogenes has been demonstrated to activate the AIM2 inflammasome (Fernandes-Alnemri et al., 2009; Hornung et al., 2009; Fernandes-Alnemri et al., 2010; Kim et al., 2010; Rathinam et al., 2010). For a comprehensive review of inflammasome activators, please refer to the recent article (Bauernfeind and Hornung, 2013). "
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