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BID ‐dependent release of mitochondrial SMAC dampens XIAP ‐mediated immunity against Shigella
Author(s) -
Andree Maria,
Seeger Jens M,
Schüll Stephan,
Coutelle Oliver,
WagnerStippich Diana,
Wiegmann Katja,
Wunderlich Claudia M,
Brinkmann Kerstin,
Broxtermann Pia,
Witt Axel,
Fritsch Melanie,
Martinelli Paola,
Bielig Harald,
Lamkemeyer Tobias,
Rugarli Elena I,
Kaufmann Thomas,
SternerKock Anja,
Wunderlich F Thomas,
Villunger Andreas,
Martins L Miguel,
Krönke Martin,
Kufer Thomas A,
Utermöhlen Olaf,
Kashkar Hamid
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201387244
Subject(s) - biology , xiap , shigella , microbiology and biotechnology , immunity , immune system , immunology , apoptosis , biochemistry , escherichia coli , caspase , gene , programmed cell death
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.