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

Nature Immunology
Si Ming ManThirumala-Devi Kanneganti

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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Citations

Dec 3, 2015·European Journal of Immunology·Si Ming ManThirumala-Devi Kanneganti
Sep 30, 2015·Proceedings of the National Academy of Sciences of the United States of America·Arun K HaldarJörn Coers
Apr 12, 2016·Communicative & Integrative Biology·Jörn Coers, Arun K Haldar
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Methods Mentioned

BETA
transfection
GTPases
confocal microscopy
Assay
ELISA

Software Mentioned

Partek Genomics Suite
Ingenuity Pathways Analysis

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