Yarovinsky Timur O, Monick Martha M, Husmann Matthias, Hunninghake Gary W
Yale University School of Medicine, Department of Immunobiology, TAC S555, 300 Cedar Street, New Haven, CT 06520, USA.
Infect Immun. 2008 Feb;76(2):571-7. doi: 10.1128/IAI.01088-07. Epub 2007 Dec 10.
Many bacterial pathogens, including Staphylococcus aureus, use a variety of pore-forming toxins as important virulence factors. Staphylococcal alpha-toxin, a prototype beta-barrel pore-forming toxin, triggers the release of proinflammatory mediators and induces primarily necrotic death in susceptible cells. However, whether host factors released in response to staphylococcal infections may increase cell resistance to alpha-toxin is not known. Here we show that prior exposure to interferons (IFNs) prevents alpha-toxin-induced membrane permeabilization, the depletion of ATP, and cell death. Moreover, pretreatment with IFN-alpha decreases alpha-toxin-induced secretion of interleukin 1beta (IL-1beta). IFN-alpha, IFN-beta, and IFN-gamma specifically protect cells from alpha-toxin, whereas tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-4 have no effects. Furthermore, we show that IFN-alpha-induced protection from alpha-toxin is not dependent on caspase-1 or mitogen-activated protein kinases, but requires protein synthesis and fatty acid synthase activity. Our results demonstrate that IFNs may increase cell resistance to staphylococcal alpha-toxin via the regulation of lipid metabolism and suggest that interferons play a protective role during staphylococcal infections.
许多细菌病原体，包括金黄色葡萄球菌，都将多种成孔毒素用作重要的毒力因子。葡萄球菌α毒素是一种典型的β桶形成孔毒素，可触发促炎介质的释放，并主要诱导易感细胞发生坏死性死亡。然而，尚不清楚宿主因葡萄球菌感染而释放的因子是否会增加细胞对α毒素的抗性。在此我们表明，预先接触干扰素（IFN）可防止α毒素诱导的膜通透性增加、ATP耗竭和细胞死亡。此外，用IFN-α预处理可减少α毒素诱导的白细胞介素1β（IL-1β）分泌。IFN-α、IFN-β和IFN-γ可特异性保护细胞免受α毒素侵害，而肿瘤坏死因子α（TNF-α）、IL-6和IL-4则无此作用。此外，我们表明IFN-α诱导的对α毒素的保护作用不依赖于半胱天冬酶-1或丝裂原活化蛋白激酶，但需要蛋白质合成和脂肪酸合酶活性。我们的结果表明，IFN可能通过调节脂质代谢来增加细胞对葡萄球菌α毒素的抗性，并表明干扰素在葡萄球菌感染期间发挥保护作用。
