Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol.
A host defense strategy against pathogens is the induction of cell death, thereby eliminating the pathogen's intracellular niche. Pyroptosis, one such form of cell death, is dependent on inflammasome activation. In a genetic screen to identify Listeria monocytogenes mutants that induced altered levels of host cell death, we identified a mutation in lmo2473 that caused hyperstimulation of IL-1beta secretion and pyroptosis following bacteriolysis in the macrophage cytosol. In addition, strains engineered to lyse in the cytosol by expression of both bacteriophage holin and lysin or induced to lyse by treatment with ampicillin stimulated pyroptosis. Pyroptosis was independent of the Nlrp3 and Nlrc4 inflammasome receptors but dependent on the inflammasome adaptor ASC and the cytosolic DNA sensor AIM2. Importantly, wild-type L. monocytogenes were also found to lyse, albeit at low levels, and trigger AIM2-dependent pyroptosis. These data suggested that pyroptosis is triggered by bacterial DNA released during cytosolic lysis.
Sauer
John-Demian
JD
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3202, USA.
Witte
Chelsea E
CE
Zemansky
Jason
J
Hanson
Bill
B
Lauer
Peter
P
Portnoy
Daniel A
DA
D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001433:Bacteriolysis; D001435:Bacteriophages / Q000235:genetics; D016923:Cell Death; D003600:Cytosol / Q000382:microbiology; D004268:DNA-Binding Proteins; D008089:Listeria monocytogenes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D009088:Mucoproteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
C540422:Aim2 protein, mouse; D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D009088:Mucoproteins; D009687:Nuclear Proteins; D014764:Viral Proteins; C096673:holin protein, Listeria monocin; C010393:lysin, gastropoda; D000667:Ampicillin