Staphylococcus aureus α-toxin modulates skin host response to viral infection.
Staphylococcus aureus α-toxin modulates skin host response to viral infection.
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DOI：
10.1016/j.jaci.2012.06.019
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发表时间：
2012-09
影响因子：
14.2
通讯作者：
Leung, Donald Y. M.
中科院分区：
文献类型：
--
作者：
Bin, Lianghua;Kim, Byung Eui;Brauweiler, Anne;Goleva, Elena;Streib, Joanne;Ji, Yinduo;Schlievert, Patrick M.;Leung, Donald Y. M.
关键词：
有疱疹性湿疹病史的特应性皮炎（AD）患者葡萄球菌定植和感染增加。然而，金黄色葡萄球菌是否改变皮肤病毒感染的结果尚未确定。我们研究了金黄色葡萄球菌毒素是否调节宿主对单纯疱疹病毒（HSV）1和牛痘病毒（VV）感染的反应，在正常人角质形成细胞（NHK）和小鼠感染模型。在孵育病毒之前，用金黄色葡萄球菌毒素处理NHK。BALB/c小鼠在VV划痕前2天接种金黄色葡萄球菌。通过实时PCR、病毒空斑形成试验和免疫荧光染色评价HSV-1和VV的病毒载量。用小干扰RNA双链体敲低α毒素细胞受体--解整合素和金属蛋白酶10（ADAM 10）的基因表达。Western blot检测ADAM 10蛋白和α毒素七聚体。我们证明，亚裂解葡萄球菌α毒素增加HSV-1和VV的病毒载量在NHK。此外，我们在体内证明，与接种同基因α毒素缺失菌株的小鼠皮肤相比，接种产α毒素金黄色葡萄球菌菌株的小鼠皮肤的VV负荷显著更大（P <0.05）。α-毒素的病毒增强作用由ADAM 10介导，并与其孔形成特性相关。此外，我们证明α-毒素促进病毒进入NHK。目前的研究引入了葡萄球菌α毒素促进病毒性皮肤感染的新概念，并提供了一种机制，通过这种机制，金黄色葡萄球菌感染可能使宿主倾向于播散性病毒感染。
Patients with atopic dermatitis (AD) with a history of eczema herpeticum have increased staphylococcal colonization and infections. However, whether Staphylococcus aureus alters the outcome of skin viral infection has not been determined. We investigated whether S aureus toxins modulated host response to herpes simplex virus (HSV) 1 and vaccinia virus (VV) infections in normal human keratinocytes (NHKs) and in murine infection models. NHKs were treated with S aureus toxins before incubation of viruses. BALB/c mice were inoculated with S aureus 2 days before VV scarification. Viral loads of HSV-1 and VV were evaluated by using real-time PCR, a viral plaque-forming assay, and immunofluorescence staining. Small interfering RNA duplexes were used to knockdown the gene expression of the cellular receptor of α-toxin, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 protein and α-toxin heptamers were detected by using Western blot assays. We demonstrate that sublytic staphylococcal α-toxin increases viral loads of HSV-1 and VV in NHKs. Furthermore, we demonstrate in vivo that the VV load is significantly greater (P < .05) in murine skin inoculated with an α-toxin–producing S aureus strain compared with murine skin inoculated with the isogenic α-toxin–deleted strain. The viral enhancing effect of α-toxin is mediated by ADAM10 and is associated with its poreforming property. Moreover, we demonstrate that α-toxin promotes viral entry in NHKs. The current study introduces the novel concept that staphylococcal α-toxin promotes viral skin infection and provides a mechanism by which S aureus infection might predispose the host toward disseminated viral infections.
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影响因子：
6.7
作者：
Di Giovine P;Settembre EC;Bhargava AK;Luftig MA;Lou H;Cohen GH;Eisenberg RJ;Krummenacher C;Carfi A
通讯作者：
Carfi A
影响因子：
8
作者：
Finelli, Lyn;Fiore, Anthony;Uyeki, Timothy
通讯作者：
Uyeki, Timothy
影响因子：
6.5
作者：
Gao, Pei-Song;Leung, Donald Y. M.;Rafaels, Nicholas M.;Boguniewicz, Mark;Hand, Tracey;Gao, Li;Hata, Tissa R.;Schneider, Lynda C.;Hanifin, Jon M.;Beaty, Terri H.;Beck, Lisa A.;Weinberg, Adriana;Barnes, Kathleen C.
通讯作者：
Barnes, Kathleen C.
影响因子：
14.2
作者：
Beck, Lisa A.;Boguniewicz, Mark;Hata, Tissa;Schneider, Lynda C.;Hanifin, Jon;Gallo, Rich;Paller, Amy S.;Lieff, Susi;Reese, Jamie;Zaccaro, Daniel;Milgrom, Henry;Barnes, Kathleen C.;Leung, Donald Y. M.
通讯作者：
Leung, Donald Y. M.
影响因子：
14.2
作者：
Boguniewicz, Mark;Leung, Donald Y. M.
通讯作者：
Leung, Donald Y. M.