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首页> 外文期刊>The Journal of Clinical Investigation: The Official Journal of the American Society for Clinical Investigation >Staphylococcus aureus toxin suppresses antigen-specific T cell responses
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Staphylococcus aureus toxin suppresses antigen-specific T cell responses

机译：金黄色葡萄球菌毒素抑制抗原特异性 T 细胞反应

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摘要

Staphylococcus aureus remains a leading cause of human infection. These infections frequently recur when the skin is a primary site of infection, especially in infants and children. In contrast, invasive staphylococcal disease is less commonly associated with reinfection, suggesting that tissue-specific mechanisms govern the development of immunity. Knowledge of how S. aureus manipulates protective immunity has been hampered by a lack of antigen-specific models to interrogate the T cell response. Using a chicken egg OVA-expressing S. aureus strain to analyze OVA-specific T cell responses, we demonstrated that primary skin infection was associated with impaired development of T cell memory. Conversely, invasive infection induced antigen-specific memory and protected against reinfection. This defect in adaptive immunity following skin infection was associated with a loss of DCs, attributable to S. aureus u-toxin (Hla) expression. Gene- and immunization-based approaches to protect against Hla during skin infection restored the T cell response. Within the human population, exposure to u-toxin through skin infection may modulate the establishment of T cell-mediated immunity, adversely affecting long-term protection. These studies prompt consideration that vaccination targeting S. aureus may be most effective if delivered prior to initial contact with the organism.
机译：金黄色葡萄球菌仍然是人类感染的主要原因。当皮肤是主要感染部位时，这些感染经常复发，尤其是在婴儿和儿童中。相比之下，侵袭性葡萄球菌病与再感染的相关性较低，这表明组织特异性机制控制着免疫力的发展。关于金黄色葡萄球菌如何操纵保护性免疫的知识由于缺乏抗原特异性模型来询问T细胞反应而受到阻碍。使用表达鸡蛋 OVA 的金黄色葡萄球菌菌株来分析 OVA 特异性 T 细胞反应，我们证明原发性皮肤感染与 T 细胞记忆发育受损有关。相反，侵袭性感染诱导抗原特异性记忆并防止再次感染。皮肤感染后适应性免疫的这种缺陷与 DC 的丢失有关，这归因于金黄色葡萄球菌 u-毒素 （Hla） 的表达。在皮肤感染期间预防Hla的基于基因和免疫的方法恢复了T细胞反应。在人群中，通过皮肤感染暴露于U毒素可能会调节T细胞介导的免疫力的建立，从而对长期保护产生不利影响。这些研究促使人们考虑，如果在初次接触病原体之前接种金黄色葡萄球菌疫苗，则针对金黄色葡萄球菌的疫苗接种可能最有效。

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