title: Cutting edge: Mycobacterium tuberculosis but not nonvirulent mycobacteria inhibits IFN-β and AIM2 inflammasome-dependent IL-1β production via its ESX-1 secretion system.
abstract: Mycobacterium tuberculosis extracellular DNA gains access to the host cell cytosol via the ESX-1 secretion system. It is puzzling that this extracellular DNA of M. tuberculosis does not induce activation of the AIM2 inflammasome because AIM2 recognizes cytosolic DNA. In this study, we show that nonvirulent mycobacteria such as Mycobacterium smegmatis induce AIM2 inflammasome activation, which is dependent on their strong induction of IFN-β production. In contrast, M. tuberculosis, but not an ESX-1-deficient mutant, inhibits the AIM2 inflammasome activation induced by either M. smegmatis or transfected dsDNA. The inhibition does not involve changes in host cell AIM2 mRNA or protein levels but led to decreased activation of caspase-1. We furthermore demonstrate that M. tuberculosis inhibits IFN-β production and signaling, which was partially responsible for the inhibition of AIM2 activation. In conclusion, we report a novel immune evasion mechanism of M. tuberculosis that involves the ESX-1-dependent, direct or indirect, suppression of the host cell AIM2 inflammasome activation during infection.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742;
authors.forename: Swati
authors.initials: S
authors.lastname: Shah
authors.forename: Amro
authors.initials: A
authors.lastname: Bohsali
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ahlbrand
authors.forename: Lalitha
authors.initials: L
authors.lastname: Srinivasan
authors.forename: Vijay A K
authors.initials: VA
authors.lastname: Rathinam
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Vogel
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.forename: Fayyaz S
authors.initials: FS
authors.lastname: Sutterwala
authors.forename: Volker
authors.initials: V
authors.lastname: Briken
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems / Q000502:physiology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C540422:Aim2 protein, mouse; D058947:Bacterial Secretion Systems; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D009687:Nuclear Proteins; D016899:Interferon-beta