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

(2015) NATURE IMMUNOLOGY. 16(5). p.467-475
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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.
Keywords
HOST-DEFENSE, GENE REGULATORY ELEMENTS, INNATE IMMUNITY, INTRACELLULAR LPS, CYTOPLASMIC DNA, TULARENSIS, CASPASE-11, RECEPTOR, INDUCTION, RESPONSES

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Citation

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Chicago
Man, Si Ming, Rajendra Karki, RK Subbarao Malireddi, Geoffrey Neale, Peter Vogel, Masahiro Yamamoto, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2015. “The Transcription Factor IRF1 and Guanylate-binding Proteins Target Activation of the AIM2 Inflammasome by Francisella Infection.” Nature Immunology 16 (5): 467–475.
APA
Man, S. M., Karki, R., Malireddi, R. S., Neale, G., Vogel, P., Yamamoto, M., Lamkanfi, M., et al. (2015). The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection. NATURE IMMUNOLOGY, 16(5), 467–475.
Vancouver
1.
Man SM, Karki R, Malireddi RS, Neale G, Vogel P, Yamamoto M, et al. The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection. NATURE IMMUNOLOGY. 2015;16(5):467–75.
MLA
Man, Si Ming et al. “The Transcription Factor IRF1 and Guanylate-binding Proteins Target Activation of the AIM2 Inflammasome by Francisella Infection.” NATURE IMMUNOLOGY 16.5 (2015): 467–475. Print.
@article{6895985,
  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.},
  author       = {Man, Si Ming and Karki, Rajendra and Malireddi, RK Subbarao and Neale, Geoffrey and Vogel, Peter and Yamamoto, Masahiro and Lamkanfi, Mohamed and Kanneganti, Thirumala-Devi},
  issn         = {1529-2908},
  journal      = {NATURE IMMUNOLOGY},
  keywords     = {HOST-DEFENSE,GENE REGULATORY ELEMENTS,INNATE IMMUNITY,INTRACELLULAR LPS,CYTOPLASMIC DNA,TULARENSIS,CASPASE-11,RECEPTOR,INDUCTION,RESPONSES},
  language     = {eng},
  number       = {5},
  pages        = {467--475},
  title        = {The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection},
  url          = {http://dx.doi.org/10.1038/ni.3118},
  volume       = {16},
  year         = {2015},
}

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