Staphylococcus aureus leukotoxin GH promotes formation of neutrophil extracellular traps.
Staphylococcus aureus leukotoxin GH promotes formation of neutrophil extracellular traps.
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DOI：
10.4049/jimmunol.1301821
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发表时间：
2013-12-15
期刊：
影响因子：
--
通讯作者：
DeLeo FR
中科院分区：
文献类型：
--
作者：
Malachowa N;Kobayashi SD;Freedman B;Dorward DW;DeLeo FR
金黄色葡萄球菌分泌许多毒力因子，促进逃避宿主免疫系统。在这些分子中有成孔溶细胞毒素，包括Panton-Valentine杀白细胞素（PVL）、白细胞毒素GH（LukGH;也称为LukAB）和DE（LukDE）以及γ-溶血素（HlgABC）。PVL和LukGH在体外具有有效的细胞溶解活性，并且这两种毒素在体内都是促炎性的。虽然在阐明这些毒素在S.尽管我们对金黄色葡萄球菌的毒力了解甚少，但我们对这些毒素促炎能力的机制以及相关的宿主对它们的反应的理解并不完整。为了解决这一知识的不足，我们评估了LukGH对人中性粒细胞增强杀菌活性的能力，并进一步研究了毒素对中性粒细胞功能的影响。我们发现，与PVL不同，LukGH不会引发人中性粒细胞增加活性氧的产生，也不会增强S的结合和/或摄取。金黄色的出乎意料的是，LukGH促进了中性粒细胞胞外陷阱（NETs）的释放，这反过来又诱捕了S，但没有杀死S。金黄色。此外，我们发现，电透化的人嗜中性粒细胞-作为一种单独的手段，以创建在中性粒细胞质膜孔-类似地诱导NET的形成，这一发现与NET可以在非特异性细胞溶解过程中形成的概念一致。我们认为LukGH促进NET形成的能力有助于炎症反应和宿主对S.金黄色葡萄球菌感染。
Staphylococcus aureus secretes numerous virulence factors that facilitate evasion of the host immune system. Among these molecules are pore-forming cytolytic toxins, including Panton-Valentine leukocidin (PVL), leukotoxins GH (LukGH; also known as LukAB) and DE (LukDE), and gamma-hemolysin (HlgABC). PVL and LukGH have potent cytolytic activity in vitro, and both toxins are proinflammatory in vivo. Although progress has been made towards elucidating the role of these toxins in S. aureus virulence, our understanding of the mechanisms that underly the proinflammatory capacity of these toxins, and the associated host response towards them, is incomplete. To address this deficiency in knowledge, we assessed the ability of LukGH to prime human PMNs for enhanced bactericidal activity and further investigated the impact of the toxin on neutrophil function. We found that unlike PVL, LukGH did not prime human neutrophils for increased production of reactive oxygen species nor did it enhance binding and/or uptake of S. aureus. Unexpectedly, LukGH promoted release of neutrophil extracellular traps (NETs), which in turn, ensnared but did not kill S. aureus. Furthermore, we found that electropermeabilization of human neutrophils—used as a separate means to create pores in the neutrophil plasma membrane—similarly induced formation of NETs, a finding consistent with the notion that NETs can form during non-specific cytolysis. We propose that the ability of LukGH to promote formation of NETs contributes to the inflammatory response and host defense against S. aureus infection.
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影响因子：
3.6
作者：
Alonzo F 3rd;Benson MA;Chen J;Novick RP;Shopsin B;Torres VJ
通讯作者：
Torres VJ
DOI：
10.4049/jimmunol.1201719
发表时间：
2012-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaplan MJ;Radic M
通讯作者：
Radic M
影响因子：
9.4
作者：
Bae, In-Gyu;Tonthat, Giang T.;Fowler, Vance G., Jr.
通讯作者：
Fowler, Vance G., Jr.
影响因子：
3.1
作者：
COLIN, DA;MAZURIER, I;FINCKBARBANCON, V
通讯作者：
FINCKBARBANCON, V
影响因子：
3.1
作者：
Aulik, Nicole A.;Hellenbrand, Katrina M.;Czuprynski, Charles J.
通讯作者：
Czuprynski, Charles J.