Grumann Dorothee, Scharf Sandra S, Holtfreter Silva, Kohler Christian, Steil Leif, Engelmann Susanne, Hecker Michael, Völker Uwe, Bröker Barbara M
Institute for Immunology and Transfusion Medicine, University of Greifswald, Greifswald, Germany.
J Immunol. 2008 Oct 1;181(7):5054-61. doi: 10.4049/jimmunol.181.7.5054.
The species Staphylococcus aureus harbors 19 superantigen gene loci, six of which are located in the enterotoxin gene cluster (egc). Although these egc superantigens are far more prevalent in clinical S. aureus isolates than non-egc superantigens, they are not a prominent cause of toxic shock. Moreover, neutralizing Abs against egc superantigens are very rare, even among carriers of egc-positive S. aureus strains. In search of an explanation, we have tested two non-exclusive hypotheses: 1) egc and non-egc superantigens have unique intrinsic properties and drive the immune system into different directions and 2) egc and non-egc superantigens are released by S. aureus under different conditions, which shape the immune response. A comparison of three egc (SEI, SElM, and SElO) and three non-egc superantigens (SEB, SElQ, and toxic shock syndrome toxin-1) revealed that both induced proliferation of human PBMC with comparable potency and elicited similar Th1/Th2-cytokine signatures. This was supported by gene expression analysis of PBMC stimulated with one representative superantigen from each group (SEI and SEB). They induced very similar transcriptional changes, especially of inflammation-associated gene networks, corresponding to a very strong Th1- and Th17-dominated immune response. In contrast, the regulation of superantigen release differed markedly between both superantigen groups. Egc-encoded proteins were secreted by S. aureus during exponential growth, while non-egc superantigens were released in the stationary phase. We conclude that the distinct biological behavior of egc and non-egc superantigens is not due to their intrinsic properties, which are very similar, but caused by their differential release by S. aureus.
金黄色葡萄球菌含有19个超抗原基因座，其中6个位于肠毒素基因簇（egc）中。尽管这些egc超抗原在临床金黄色葡萄球菌分离株中比非egc超抗原更为普遍，但它们并非中毒性休克的主要原因。此外，针对egc超抗原的中和抗体非常罕见，即使在egc阳性金黄色葡萄球菌菌株携带者中也是如此。为了寻找解释，我们测试了两个并非相互排斥的假设：1）egc和非egc超抗原具有独特的内在特性，会将免疫系统导向不同方向；2）egc和非egc超抗原在不同条件下由金黄色葡萄球菌释放，这塑造了免疫反应。对三种egc超抗原（SEI、SElM和SElO）和三种非egc超抗原（SEB、SElQ和中毒性休克综合征毒素-1）的比较显示，两者诱导人外周血单核细胞增殖的能力相当，并且引发了相似的Th1/Th2细胞因子特征。这得到了用每组一种代表性超抗原（SEI和SEB）刺激的外周血单核细胞基因表达分析的支持。它们诱导了非常相似的转录变化，特别是与炎症相关的基因网络的变化，对应于非常强烈的以Th1和Th17为主导的免疫反应。相比之下，两种超抗原组之间超抗原释放的调节存在明显差异。egc编码的蛋白质在指数生长期由金黄色葡萄球菌分泌，而非egc超抗原在稳定期释放。我们得出结论，egc和非egc超抗原不同的生物学行为并非由于它们非常相似的内在特性所致，而是由金黄色葡萄球菌对它们不同的释放方式引起的。
