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 α-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 α-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.

中文翻译：

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金黄色葡萄球菌毒素抑制抗原特异性T细胞反应

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，尤其是在婴儿和儿童中，这些感染经常复发。相反，侵袭性葡萄球菌病与再感染较少见，这表明组织特异性机制控制着免疫的发展。关于S的知识。由于缺乏抗原特异性模型来询问T细胞反应，金黄色素操纵性保护性免疫受到阻碍。使用鸡蛋表达OVA的小号。金黄色菌株分析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。这个缺陷在适应性免疫以下皮肤感染与DC的损失，归因于相关联的小号。金黄色素α-毒素（Hla）表达。基于基因和免疫的方法可在皮肤感染期间预防Hla，从而恢复了T细胞反应。在人群中，通过皮肤感染暴露于α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针对S的疫苗接种。金黄色 如果在与生物体初次接触之前进行递送，可能会最有效。