title: The AIM2 inflammasome is critical for innate immunity to Francisella tularensis.
abstract: Francisella tularensis, the causative agent of tularemia, infects host macrophages, which triggers production of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-18. We elucidate here how host macrophages recognize F. tularensis and elicit this proinflammatory response. Using mice deficient in the DNA-sensing inflammasome component AIM2, we demonstrate here that AIM2 is required for sensing F. tularensis. AIM2-deficient mice were extremely susceptible to F. tularensis infection, with greater mortality and bacterial burden than that of wild-type mice. Caspase-1 activation, IL-1beta secretion and cell death were absent in Aim2(-/-) macrophages in response to F. tularensis infection or the presence of cytoplasmic DNA. Our study identifies AIM2 as a crucial sensor of F. tularensis infection and provides genetic proof of its critical role in host innate immunity to intracellular pathogens.
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Fernandes-Alnemri
authors.forename: Je-Wook
authors.initials: JW
authors.lastname: Yu
authors.forename: Christine
authors.initials: C
authors.lastname: Juliana
authors.forename: Leobaldo
authors.initials: L
authors.lastname: Solorzano
authors.forename: Seokwon
authors.initials: S
authors.lastname: Kang
authors.forename: Jianghong
authors.initials: J
authors.lastname: Wu
authors.forename: Pinaki
authors.initials: P
authors.lastname: Datta
authors.forename: Margaret
authors.initials: M
authors.lastname: McCormick
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Erin
authors.initials: E
authors.lastname: McDermott
authors.forename: Laurence
authors.initials: L
authors.lastname: Eisenlohr
authors.forename: Carlisle P
authors.initials: CP
authors.lastname: Landel
authors.forename: Emad S
authors.initials: ES
authors.lastname: Alnemri
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000276:immunology; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005604:Francisella tularensis / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D055503:Protein Multimerization; D014406:Tularemia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C540422:Aim2 protein, mouse; D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D053583:Interleukin-1beta; C494233:Irf3 protein, mouse; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D007770:L-Lactate Dehydrogenase; D020170:Caspase 1