Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
J Immunol. 2010 Jan 1;184(1):420-5. doi: 10.4049/jimmunol.0902865. Epub 2009 Nov 30.
The human pathogen Staphylococcus aureus produces several complement-evasion molecules that enable the bacterium to withstand the host immune response. The human-specific staphylococcal complement inhibitor (SCIN) blocks the central C3 convertase enzymes that trigger critical complement functions, such as C3b deposition, phagocytosis, and C5a generation. SCIN effectively blocks the conversion of C3 by alternative pathway C3 convertases (C3bBb), but also induces dimerization of these enzymes. In this study, we show that formation of dimeric convertases by SCIN is important for S. aureus immune evasion because it modulates complement recognition by phagocytic receptors. Dimeric, but not monomeric, SCIN convertases showed an impaired binding to complement receptor 1 and the complement receptor of the Ig superfamily. The dimerization site of SCIN is essential for its strong antiphagocytic properties. These studies provide critical insights into the unique immune-evasion strategies used by S. aureus.
人体病原体金黄色葡萄球菌产生了几种补体逃逸分子，使细菌能够抵御宿主的免疫反应。人源特异性葡萄球菌补体抑制剂 (SCIN) 可阻断触发关键补体功能的中央 C3 转化酶，如 C3b 沉积、吞噬作用和 C5a 生成。SCIN 可有效阻断替代途径 C3 转化酶 (C3bBb) 的 C3 转化，但也诱导这些酶的二聚化。在这项研究中，我们表明，SCIN 形成二聚转化酶对于金黄色葡萄球菌的免疫逃避很重要，因为它调节吞噬受体对补体的识别。二聚化，而不是单体化，的 SCIN 转化酶显示与补体受体 1 和 Ig 超家族的补体受体的结合能力受损。SCIN 的二聚化位点对其强大的抗吞噬特性至关重要。这些研究为金黄色葡萄球菌使用的独特免疫逃避策略提供了重要的见解。
