title: Cutting edge: Cytosolic bacterial DNA activates the inflammasome via Aim2.
abstract: Pathogens are detected by pattern recognition receptors that, upon activation, orchestrate an appropriate immune response. The TLRs and the nucleotide-binding oligomerization domain-like receptors (NLRs) are prototypic pattern recognition receptors that detect extracellular and cytosolic pathogens, respectively. Listeria monocytogenes has both extracellular and cytosolic phases and is detected in the cytosol by members of the NLR family. These include two NLR members, NLRC4 and NLRP3, that, upon detection of cytosolic L. monocytogenes, induce the assembly of the inflammasome. Inflammasomes serve as platforms for the activation of the protease caspase 1, which mediates the processing and secretion of pro-IL-1beta and pro-IL-18. We previously provided evidence that L. monocytogenes is also detected by a third inflammasome. We now use biochemical and genetic approaches to demonstrate that the third detector senses bacterial DNA and identify it as Aim2, a receptor that has previously been shown to detect viral DNA.
authors.affiliation: Institute for Systems Biology, Seattle, WA 98103, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Warren
authors.forename: Abraham
authors.initials: A
authors.lastname: Armstrong
authors.forename: M Kristina
authors.initials: MK
authors.lastname: Hamilton
authors.forename: Dat P
authors.initials: DP
authors.lastname: Mao
authors.forename: Irina A
authors.initials: IA
authors.lastname: Leaf
authors.forename: Edward A
authors.initials: EA
authors.lastname: Miao
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003600:Cytosol / Q000276:immunology / Q000382:microbiology; D004269:DNA, Bacterial / Q000276:immunology*; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D054884:Host-Pathogen Interactions; D053583:Interleukin-1beta / Q000378:metabolism; D007739:L Cells; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D034622:RNA Interference
chemical_list: C540422:Aim2 protein, mouse; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D009687:Nuclear Proteins