Interferon-γ Protects from Staphylococcal Alpha Toxin-Induced Keratinocyte Death through Apolipoprotein L1
Interferon-γ Protects from Staphylococcal Alpha Toxin-Induced Keratinocyte Death through Apolipoprotein L1
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DOI：
10.1016/j.jid.2015.12.006
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发表时间：
2016-03-01
影响因子：
6.5
通讯作者：
Leung, Donald Y. M.
中科院分区：
文献类型：
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作者：
Brauweiler, Anne M.;Goleva, Elena;Leung, Donald Y. M.
金黄色葡萄球菌是一种经常感染皮肤的细菌病原体，通过其主要毒力因子阿尔法毒素引起皮肤损伤和细胞破坏。在这里，我们显示干扰素-伽马(干扰素-伽马)保护角质形成细胞免受葡萄球菌α毒素诱导的细胞死亡。我们发现，干扰素-γ阻止了阿尔法毒素结合，并减少了阿尔法毒素受体-去整合素和金属蛋白酶10(ADAM10)的表达。我们确定，干扰素-γ介导的阿尔法毒素抗性的机制涉及自噬的诱导，这是细胞对亚致死性损伤的适应过程。我们发现，干扰素-γ能有效地刺激主要的自噬效应因子轻链3(Lc3)的激活。这一过程依赖于载脂蛋白L1的上调。小干扰RNA耗尽载脂蛋白L1显著增加α毒素诱导的致死率并抑制轻链3的激活。我们认为，干扰素-γ通过载脂蛋白L1诱导的自噬保护角质形成细胞免受金黄色葡萄球菌毒素的致死作用。
Staphylococcus aureus is a bacterial pathogen that frequently infects the skin, causing lesions and cell destruction through its primary virulence factor, alpha toxin. Here we show that interferon gamma (IFN-gamma) protects human keratinocytes from cell death induced by staphylococcal alpha toxin. We find that IFN-gamma prevents alpha toxin binding and reduces expression of the alpha toxin receptor, a disintegrin and metalloproteinase 10 (ADAM10). We determine that the mechanism for IFN-gamma-mediated resistance to alpha toxin involves the induction of autophagy, a process of cellular adaptation to sublethal damage. We find that IFN-gamma potently stimulates activation of the primary autophagy effector, light chain 3 (LC3). This process is dependent on upregulation of apolipoprotein L1. Depletion of apolipoprotein L1 by small interfering RNA significantly increases alpha toxin-induced lethality and inhibits activation of light chain 3. We conclude that IFN-gamma plays a significant role in protecting human keratinocytes from the lethal effects of staphylococcal alpha toxin through apolipoprotein L1-induced autophagy.