Functional basis for complement evasion by staphylococcal superantigen-like 7.
Functional basis for complement evasion by staphylococcal superantigen-like 7.
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DOI：
10.1111/j.1462-5822.2010.01486.x
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发表时间：
2010-10
影响因子：
3.4
通讯作者：
de Haas CJ
中科院分区：
文献类型：
--
作者：
Bestebroer J;Aerts PC;Rooijakkers SH;Pandey MK;Köhl J;van Strijp JA;de Haas CJ
人类病原体金黄色葡萄球菌具有过多的毒力因子，这些毒力因子促进其在宿主中的定殖和存活。在这些免疫调节剂中，葡萄球菌超抗原样（SSL）蛋白包括14个小的分泌分子家族，其似乎干扰宿主先天免疫系统。已描述SSL 7结合免疫球蛋白A（伊加）和补体C5，从而抑制IgA-FcαRI结合和E.杆菌与C5 b-9介导的裂解相反，由于C5 a的产生对于针对葡萄球菌的免疫防御至关重要，因此我们研究了SSL 7对葡萄球菌诱导的C5 a介导的效应的影响。在这里，我们表明，SSL 7抑制葡萄球菌调理作用诱导的C5 a生成，其IgA结合能力略有增强。此外，我们证明了SSL 7对人全血中葡萄球菌清除的强保护活性。SSL 7对C5 a诱导的S.金黄色葡萄球菌和氧化爆发在体外全血炎症模型。此外，我们发现SSL 7影响补体激活的所有三个途径，并通过干扰其与C5转化酶的结合来抑制C5的切割。最后，还在体内证实了SSL 7的作用。在免疫复合物腹膜炎的鼠模型中，SSL 7消除了小鼠腹膜中C5 a驱动的中性粒细胞内流。
The human pathogen Staphylococcus aureus has a plethora of virulence factors that promote its colonization and survival in the host. Among such immune modulators are staphylococcal superantigen-like (SSL) proteins, comprising a family of 14 small, secreted molecules that seem to interfere with the host innate immune system. SSL7 has been described to bind immunoglobulin A (IgA) and complement C5, thereby inhibiting IgA-FcαRI binding and serum killing of E. coli. As C5a generation, in contrast to C5b-9-mediated lysis, is crucial for immune defense against staphylococci, we investigated the impact of SSL7 on staphylococcal-induced C5a-mediated effects. Here, we show that SSL7 inhibits C5a generation induced by staphylococcal opsonization, slightly enhanced by its IgA-binding capacity. Moreover, we demonstrate a strong protective activity of SSL7 against staphylococcal clearance in human whole blood. SSL7 strongly inhibited the C5a-induced phagocytosis of S. aureus and oxidative burst in an in vitro whole blood inflammation model. Furthermore, we found that SSL7 affects all three pathways of complement activation and inhibits the cleavage of C5 by interference of its binding to C5 convertases. Finally, SSL7 effects were also demonstrated in vivo. In a murine model of immune complex peritonitis, SSL7 abrogated the C5a-driven influx of neutrophils in mouse peritoneum.
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影响因子：
4.4
作者：
Godau, J;Heller, T;Köhl, J
通讯作者：
Köhl, J
DOI：
10.1084/jem.20031636
发表时间：
2004-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
de Haas CJ;Veldkamp KE;Peschel A;Weerkamp F;Van Wamel WJ;Heezius EC;Poppelier MJ;Van Kessel KP;van Strijp JA
通讯作者：
van Strijp JA
DOI：
10.1084/jem.20070818
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jongerius I;Köhl J;Pandey MK;Ruyken M;van Kessel KP;van Strijp JA;Rooijakkers SH
通讯作者：
Rooijakkers SH
影响因子：
20.3
作者：
Bestebroer, Jovanka;Poppelier, Miriam J. J. G.;de Haas, Carla J. C.
通讯作者：
de Haas, Carla J. C.
影响因子：
64.8
作者：
Hopken, UE;Lu, B;Gerard, C
通讯作者：
Gerard, C