Department of Pediatrics, University of Chicago, Chicago Illinois, USA.
Infect Immun. 2014 May;82(5):2125-34. doi: 10.1128/IAI.01491-14. Epub 2014 Mar 10.
Although many microbial infections elicit an adaptive immune response that can protect against reinfection, it is generally thought that Staphylococcus aureus infections fail to generate protective immunity despite detectable T and B cell responses. No vaccine is yet proven to prevent S. aureus infections in humans, and efforts to develop one have been hampered by a lack of animal models in which protective immunity occurs. Our results describe a novel mouse model of protective immunity against recurrent infection, in which S. aureus skin and soft tissue infection (SSTI) strongly protected against secondary SSTI in BALB/c mice but much less so in C57BL/6 mice. This protection was dependent on antibody, because adoptive transfer of immune BALB/c serum or purified antibody into either BALB/c or C57BL/6 mice resulted in smaller skin lesions. We also identified an antibody-independent mechanism, because B cell-deficient mice were partially protected against secondary S. aureus SSTI and adoptive transfer of T cells from immune BALB/c mice resulted in smaller lesions upon primary infection. Furthermore, neutralization of interleukin-17A (IL-17A) abolished T cell-mediated protection in BALB/c mice, whereas neutralization of gamma interferon (IFN-γ) enhanced protection in C57BL/6 mice. Therefore, protective immunity against recurrent S. aureus SSTI was advanced by antibody and the Th17/IL-17A pathway and prevented by the Th1/IFN-γ pathway, suggesting that targeting both cell-mediated and humoral immunity might optimally protect against secondary S. aureus SSTI. These findings also highlight the importance of the mouse genetic background in the development of protective immunity against S. aureus SSTI.
尽管许多微生物感染会引发适应性免疫反应，从而防止再次感染，但一般认为金黄色葡萄球菌感染不会产生保护性免疫，尽管可检测到 T 和 B 细胞反应。目前还没有证明有疫苗可以预防人类的金黄色葡萄球菌感染，而开发疫苗的努力因缺乏保护性免疫发生的动物模型而受阻。我们的研究结果描述了一种针对复发性感染的保护性免疫的新型小鼠模型，在该模型中，金黄色葡萄球菌皮肤和软组织感染（SSTI）强烈保护 BALB/c 小鼠免受二次 SSTI，但对 C57BL/6 小鼠的保护作用要小得多。这种保护依赖于抗体，因为将免疫的 BALB/c 血清或纯化的抗体过继转移到 BALB/c 或 C57BL/6 小鼠中，会导致皮肤损伤更小。我们还确定了一种抗体非依赖性机制，因为 B 细胞缺陷小鼠对二次金黄色葡萄球菌 SSTI 有部分保护作用，并且从免疫的 BALB/c 小鼠过继转移 T 细胞会导致原发性感染时皮肤损伤更小。此外，中和白细胞介素-17A（IL-17A）可消除 BALB/c 小鼠中 T 细胞介导的保护作用，而中和γ干扰素（IFN-γ）可增强 C57BL/6 小鼠的保护作用。因此，针对复发性金黄色葡萄球菌 SSTI 的保护性免疫是由抗体和 Th17/IL-17A 途径推进的，而由 Th1/IFN-γ 途径阻止的，这表明靶向细胞免疫和体液免疫可能是预防二次金黄色葡萄球菌 SSTI 的最佳方法。这些发现还强调了小鼠遗传背景在金黄色葡萄球菌 SSTI 保护性免疫中的重要性。
