BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella

被引：47

作者：

Andree, Maria ^{[1
,2
,3
]}

Seeger, Jens M. ^{[1
,2
,3
]}

Schuell, Stephan ^{[1
,2
,3
]}

Coutelle, Oliver ^{[1
,2
,3
]}

Wagner-Stippich, Diana ^{[1
,2
,3
]}

Wiegmann, Katja ^{[1
]}

Wunderlich, Claudia M. ^{[3
,4
]}

Brinkmann, Kerstin ^{[1
,2
,3
]}

Broxtermann, Pia ^{[1
,2
,3
]}

Witt, Axel ^{[1
,2
,3
]}

Fritsch, Melanie ^{[1
,2
,3
]}

Martinelli, Paola ^{[2
,3
]}

Bielig, Harald ^{[1
]}

Lamkemeyer, Tobias ^{[3
]}

Rugarli, Elena I. ^{[2
,3
,4
]}

Kaufmann, Thomas ^{[5
]}

Sterner-Kock, Anja ^{[6
]}

Wunderlich, F. Thomas ^{[3
,4
]}

Villunger, Andreas ^{[7
]}

Martins, L. Miguel ^{[8
]}

Kroenke, Martin ^{[1
,2
,3
]}

Kufer, Thomas A. ^{[1
]}

Utermoehlen, Olaf ^{[1
,2
]}

Kashkar, Hamid ^{[1
,2
,3
]}

机构：

[1] Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50931 Cologne, Germany

[2] Univ Cologne, CMMC, D-50931 Cologne, Germany

[3] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany

[4] Max Planck Inst Metab Res, Cologne, Germany

[5] Univ Bern, Inst Pharmacol, Bern, Switzerland

[6] Univ Cologne, CEM, D-50931 Cologne, Germany

[7] Med Univ Innsbruck, Bioctr, Div Dev Immunol, A-6020 Innsbruck, Austria

[8] Cell Death Regulat Lab, MRC Toxicol Unit, Leicester, Leics, England

来源：

EMBO JOURNAL | 2014年 / 33卷 / 19期

关键词：

inflammation; mitochondria; Shigella; SMAC; XIAP; NF-KAPPA-B; CELL-DEATH; ACTIVATION; EXPRESSION; APOPTOSIS; PROTEIN; INFLAMMATION; DEFICIENCY; INFECTION; INHIBITION;

D O I：

10.15252/embj.201387244

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The X-linked inhibitor of apoptosis protein (XIAP) is a potent caspase inhibitor, best known for its anti-apoptotic function in cancer. During apoptosis, XIAP is antagonized by SMAC, which is released from the mitochondria upon caspase-mediated activation of BID. Recent studies suggest that XIAP is involved in immune signaling. Here, we explore XIAP as an important mediator of an immune response against the enteroinvasive bacterium Shigella flexneri, both in vitro and in vivo. Our data demonstrate for the first time that Shigella evades the XIAP-mediated immune response by inducing the BID-dependent release of SMAC from the mitochondria. Unlike apoptotic stimuli, Shigella activates the calpain-dependent cleavage of BID to trigger the release of SMAC, which antagonizes the inflammatory action of XIAP without inducing apoptosis. Our results demonstrate how the cellular death machinery can be subverted by an invasive pathogen to ensure bacterial colonization.

引用

页码：2171 / 2187

页数：17

共 56 条

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Shigella IpaH0722 E3 Ubiquitin Ligase Effector Targets TRAF2 to Inhibit PKC-NF-κB Activity in Invaded Epithelial Cells [J].