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

被引：295

作者：

Man, Si Ming ^{[1
,2
]}

Karki, Rajendra ^{[1
]}

Malireddi, R. K. Subbarao ^{[1
]}

Neale, Geoffrey ^{[3
]}

Vogel, Peter ^{[4
,5
]}

Yamamoto, Masahiro ^{[6
]}

Lamkanfi, Mohamed ^{[7
,8
]}

Kanneganti, Thirumala-Devi ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA

[2] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia

[3] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA

[4] St Jude Childrens Res Hosp, Anim Resources Ctr, Memphis, TN 38105 USA

[5] St Jude Childrens Res Hosp, Vet Pathol Core, Memphis, TN 38105 USA

[6] Osaka Univ, Dept Microbiol & Immunol, Osaka, Japan

[7] Vlaams Inst Biotechnol, Dept Med Prot Res, Ghent, Belgium

[8] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium

来源：

NATURE IMMUNOLOGY | 2015年 / 16卷 / 05期

基金：

美国国家卫生研究院; 欧洲研究理事会; 英国医学研究理事会;

关键词：

INNATE IMMUNITY; HOST-DEFENSE; TULARENSIS; INDUCTION; NLRP3; TOLL; DISRUPTION; MECHANISMS; REGULATOR; CASPASE-1;

D O I：

10.1038/ni.3118

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：467 / U174

页数：11

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[1] Intracellular Trafficking of Guanylate-Binding Proteins Is Regulated by Heterodimerization in a Hierarchical Manner [J].

Britzen-Laurent, Nathalie ;

Bauer, Michael ;

Berton, Valeria ;

Fischer, Nicole ;

Syguda, Adrian ;

Reipschlaeger, Simone ;

Naschberger, Elisabeth ;

Herrmann, Christian ;

Stuerzl, Michael .

PLOS ONE, 2010, 5 (12)

[2] Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1 [J].

Broz, Petr ;

Ruby, Thomas ;

Belhocine, Kamila ;

Bouley, Donna M. ;

Kayagaki, Nobuhiko ;

Dixit, Vishva M. ;

Monack, Denise M. .

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[3] An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome [J].

Buerckstuemmer, Tilmann ;

Baumann, Christoph ;

Blueml, Stephan ;

Dixit, Evelyn ;

Duernberger, Gerhard ;

Jahn, Hannah ;

Planyavsky, Melanie ;

Bilban, Martin ;

Colinge, Jacques ;

Bennett, Keiryn L. ;

Superti-Furga, Giulio .

NATURE IMMUNOLOGY, 2009, 10 (03) :266-272

[4] Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication [J].

Checroun, Claire ;

Wehrly, Tara D. ;

Fischer, Elizabeth R. ;

Hayes, Stanley F. ;

Celli, Jean .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (39) :14578-14583

[5] The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease [J].

Connolly, Dympna J. ;

Bowie, Andrew G. .

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[6] Cytosolic DNA Triggers Inflammasome Activation in Keratinocytes in Psoriatic Lesions [J].

Dombrowski, Yvonne ;

Peric, Mark ;

Koglin, Sarah ;

Kammerbauer, Claudia ;

Goess, Christine ;

Anz, David ;

Simanski, Maren ;

Glaeser, Regine ;

Harder, Juergen ;

Hornung, Veit ;

Gallo, Richard L. ;

Ruzicka, Thomas ;

Besch, Robert ;

Schauber, Juergen .

SCIENCE TRANSLATIONAL MEDICINE, 2011, 3 (82)

[7] Targeted disruption of the mouse STAT1 results in compromised innate immunity to viral disease [J].

Durbin, JE ;

Hackenmiller, R ;

Simon, MC ;

Levy, DE .

CELL, 1996, 84 (03) :443-450

[8] In vivo clearance of an intracellular bacterium, Francisella tularensis LVS, is dependent on the p40 subunit of interleukin-12 (IL-12) but not on IL-12 p70 [J].

Elkins, KL ;

Cooper, A ;

Colombini, SM ;

Cowley, SC ;

Kieffer, TL .

INFECTION AND IMMUNITY, 2002, 70 (04) :1936-1948

[9] The AIM2 inflammasome is critical for innate immunity to Francisella tularensis [J].

Fernandes-Alnemri, Teresa ;

Yu, Je-Wook ;

Juliana, Christine ;

Solorzano, Leobaldo ;

Kang, Seokwon ;

Wu, Jianghong ;

Datta, Pinaki ;

McCormick, Margaret ;

Huang, Lan ;

McDermott, Erin ;

Eisenlohr, Laurence ;

Landel, Carlisle P. ;

Alnemri, Emad S. .

NATURE IMMUNOLOGY, 2010, 11 (05) :385-394

[10] AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA [J].

Fernandes-Alnemri, Teresa ;

Yu, Je-Wook ;

Datta, Pinaki ;

Wu, Jianghong ;

Alnemri, Emad S. .

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