Abstract:
:After phagocytosis by macrophages, Staphylococcus aureus evades killing in an α-toxin-dependent manner, and then prevents apoptosis of infected cells by upregulating expression of antiapoptotic genes like MCL-1 (myeloid cell leukemia-1). Here, using purified α-toxin and a set of hla-deficient strains, we show that α-toxin is critical for the induction of MCL-1 expression and the cytoprotection of infected macrophages. Extracellular or intracellular treatment of macrophages with α-toxin alone did not induce cytoprotection conferred by increased Mcl-1, suggesting that the process is dependent on the production of α-toxin by intracellular bacteria. The increased expression of MCL-1 in infected cells was associated with enhanced NFκB activation, and subsequent IL-6 secretion. This effect was only partially inhibited by blocking TLR2, which suggests the participation of intracellular receptors in the specific recognition of S. aureus strains secreting α-toxin. Thus, S. aureus recognition by intracellular receptors and/or activation of downstream pathways leading to Mcl-1 expression is facilitated by α-toxin released by intracellular bacteria which permeabilize phagosomes, ensuring pathogen access to the cytoplasmatic compartment. Given that the intracellular survival of S. aureus depends on α-toxin, we propose a novel role for this agent in the protection of the intracellular niche, and further dissemination of staphylococci by infected macrophages.
journal_name
J Innate Immunjournal_title
Journal of innate immunityauthors
Koziel J,Chmiest D,Bryzek D,Kmiecik K,Mizgalska D,Maciag-Gudowska A,Shaw LN,Potempa Jdoi
10.1159/000368048subject
Has Abstractpub_date
2015-01-01 00:00:00pages
187-98issue
2eissn
1662-811Xissn
1662-8128pii
000368048journal_volume
7pub_type
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