The transcription factor IRF1 and guanylate-binding proteins target AIM2 inflammasome activation by Francisella infection
نویسندگان
چکیده
Inflammasomes are critical for mounting host defense against pathogens. The molecular mechanisms controlling activation of the AIM2 inflammasome in response to different cytosolic pathogens is unclear. Here, we show that the transcription factor IRF1 is the upstream molecule leading to AIM2 inflammasome activation during Francisella novicida infection, whereas engagement of the AIM2 inflammasome by mouse cytomegalovirus or transfected dsDNA did not require IRF1. F. novicida infection detected by the cGAS-STING pathway induces type I interferon-dependent expression of IRF1, which drives the expression of guanylate-binding proteins (GBPs) leading to intracellular bacterial killing and DNA release. These results reveal a specific requirement for IRF1 and GBPs in the liberation of DNA for AIM2 sensing depending on the pathogen encountered by the cell. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence to: Thirumala-Devi Kanneganti, Department of Immunology, St Jude Children’s Research Hospital, MS #351, 570, St. Jude Place, Suite E7004, Memphis TN 38105-2794, Tel: (901) 595-3634; Fax. (901) 595-5766. [email protected]. Author Contributions S.M.M., R.K. and T.-D.K. designed the study. S.M.M., M.L. and T.-D.K. wrote the manuscript. S.M.M., R.K., R.K.S.M., G.N., and P.V. performed the experiments and analyzed the data; M.Y. contributed reagents. COMPETING INTERESTS STATEMENT The authors declare no conflict of interest. HHS Public Access Author manuscript Nat Immunol. Author manuscript; available in PMC 2015 November 01. Published in final edited form as: Nat Immunol. 2015 May ; 16(5): 467–475. doi:10.1038/ni.3118. A uhor M anscript
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