The Janus Face of α-Toxin: A Potent Mediator of Cytoprotection in Staphylococci-Infected Macrophages
The Janus Face of α-Toxin: A Potent Mediator of Cytoprotection in Staphylococci-Infected Macrophages
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DOI：
10.1159/000368048
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发表时间：
2015-01-01
影响因子：
5.3
通讯作者：
Potempa, Jan
中科院分区：
文献类型：
--
作者：
Koziel, Joanna;Chmiest, Daniela;Potempa, Jan
After phagocytosis by macrophages, Staphylococcus aureus evades killing in an alpha-toxin-dependent manner, and then prevents apoptosis of infected cells by upregulating expression of antiapoptotic genes like MCL-7 (myeloid cell leukemia-1). Here, using purified alpha-toxin and a set of h/a-deficient strains, we show that alpha-toxin is critical for the induction of MCL-1 expression and the cytoprotection of infected macrophages. Extracellular or intracellular treatment of macrophages with a-toxin alone did not induce cytoprotection conferred by increased Mcl-1, suggesting that the process is dependent on the production of alpha-toxin by intracellular bacteria. The increased expression of MCL-1 in infected cells was associated with enhanced NF kappa B 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 alpha-toxin. Thus, S. aureus recognition by intracellular receptors and/or activation of downstream pathways leading to Mcl-1 expression is facilitated by alpha-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 alpha-toxin, we propose a novel role for this agent in the protection of the intracellular niche, and further dissemination of staphylococci by infected macrophages. (C) 2014 S. Karger AG, Basel
