The Transcription Factor IRF1 and Guanylate-binding Proteins Target Activation of the AIM2 Inflammasome by Francisella Infection

Overview

Journal Nat Immunol

Date 2015 Mar 17

PMID 25774715

Citations 221

Authors

Si Ming Man

Rajendra Karki

R K Subbarao Malireddi

Geoffrey Neale

Peter Vogel

Masahiro Yamamoto

Mohamed Lamkanfi

Thirumala-Devi Kanneganti

Affiliations

Soon will be listed here.

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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