A mutant of staphylococcal enterotoxin C devoid of bacterial superantigenic activity elicits a Th2 immune response for protection against Staphylococcus aureus infection
A mutant of staphylococcal enterotoxin C devoid of bacterial superantigenic activity elicits a Th2 immune response for protection against Staphylococcus aureus infection
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DOI：
10.1128/iai.73.1.174-180.2005
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Nakane, A
中科院分区：
文献类型：
--
作者：
Hu, DL;Cui, JC;Nakane, A
金黄色葡萄球菌肠毒素C（SEC）是一种细菌超抗原外毒素，通常由侵袭性金黄色葡萄球菌分离株产生，尤其是耐甲氧西林菌株和动物疾病分离株。我们构建并表达了一个无毒的突变体SEC（mSEC），并研究了用mSEC免疫是否能保护S。金黄色葡萄球菌感染。用mSEC免疫小鼠并用活的S.金黄色。mSEC免疫小鼠的器官中的细菌计数显著低于对照组的相应值，并且存活率高于对照组的相应值。用mSEC免疫强烈诱导T辅助细胞2型抗体、免疫球蛋白G1和免疫球蛋白G2 b的产生。免疫小鼠经S.金黄色葡萄球菌的免疫小鼠比对照小鼠中的免疫小鼠的IFN-γ的产生显著降低，而γ干扰素（IFN-γ）的产生在免疫小鼠中显著降低。用热灭活S刺激的脾细胞培养物中的细胞因子反应。金黄色葡萄球菌或SEC显示，用mSEC免疫在体外抑制IFN-γ产生并上调IL-10产生。此外，IFN-γ和肿瘤坏死因子α在体外的生产显着抑制mSEC免疫小鼠的血清，但不从对照小鼠的血清。这些结果表明，用缺乏超抗原特性的mSEC免疫提供了针对S.金黄色葡萄球菌感染，保护作用可能是由SEC特异性中和抗体介导的。
Staphylococcal enterotoxin C (SEC), a bacterial superantigenic exotoxin, is commonly produced by invasive Staphylococcus aureus isolates, especially methicillin-resistant strains and isolates from animal diseases. We constructed and expressed a nontoxic mutant SEC (mSEC) and investigated whether immunization with mSEC, which is devoid of superantigenic activity, can protect against S. aureus infection. Mice were immunized with mSEC and challenged with viable S. aureus. The bacterial counts in the organs of mSEC-immunized mice were significantly lower and the survival rate was higher than the corresponding values for the control group. Immunization with mSEC strongly induced the production of T-helper 2 type antibodies, immunoglobulin G1, and immunoglobulin G2b. The production of interieukin-10 (IL-10) and IL-4 was significantly greater in immunized mice challenged with S. aureus than in the control mice, whereas the production of gamma interferon (IFN-gamma) was significantly decreased in the immunized mice. The cytokine response in a spleen cell culture that was stimulated with heat-killed S. aureus or SEC showed that immunization with mSEC inhibited IFN-gamma production and up-regulated IL-10 production in vitro. Furthermore, IFN-gamma and tumor necrosis factor alpha production in vitro was significantly inhibited by sera from mSEC-immunized mice but not by sera from control mice. These results suggest that immunization with mSEC devoid of superantigenic properties provides protection against S. aureus infection and that the protection might be mediated by SEC-specific neutralizing antibodies.