2. Academic Validation
  3. The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection

The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection

  • Nat Immunol. 2015 May;16(5):467-75. doi: 10.1038/ni.3118.
Si Ming Man 1,  Rajendra Karki 2,  R K Subbarao Malireddi 2,  Geoffrey Neale 3,  Peter Vogel 4,  Masahiro Yamamoto 5,  Mohamed Lamkanfi 6,  Thirumala-Devi Kanneganti 2
Affiliations

Affiliations

  • 1 1] Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
  • 2 Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • 3 Hartwell Center for Bioinformatics &Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • 4 Animal Resources Center and the Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • 5 Department of Microbiology and Immunology, Osaka University, Osaka, Japan.
  • 6 1] Department of Medical Protein Research, Vlaams Instituut voor Biotechnologie, Ghent, Belgium. [2] Department of Biochemistry, Ghent University, Ghent, Belgium.
PMID: 25774715 DOI: 10.1038/ni.3118
Abstract

Inflammasomes are critical for mounting host defense against pathogens. The molecular mechanisms that control activation of the AIM2 inflammasome in response to different cytosolic pathogens remain unclear. Here we found that the transcription factor IRF1 was required for activation of the AIM2 inflammasome during Infection with the Francisella tularensis subspecies novicida (F. novicida), whereas engagement of the AIM2 inflammasome by mouse cytomegalovirus (MCMV) or transfected double-stranded DNA did not require IRF1. Infection of F. novicida detected by the DNA sensor cGAS and its adaptor STING induced type I interferon-dependent expression of IRF1, which drove the expression of guanylate-binding proteins (GBPs); this led to intracellular killing of bacteria and DNA release. Our results reveal a specific requirement for IRF1 and GBPs in the liberation of DNA for sensing by AIM2 depending on the pathogen encountered by the cell.

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