Humans do not usually develop effective immunity to Staphylococcus aureus reinfection. Using a murine model that mimics human infection, we show that lack of protective immunity to S. aureus systemic reinfection is associated with robust interleukin-10 (IL-10) production and impaired protective Th17 responses. In dendritic cell co-culture assays, priming with S. aureus promotes robust T cell proliferation, but limits Th cells polarization and production of IL-1β and other cytokines important for Th1 and Th17 differentiation. We show that O-acetylation of peptidoglycan, a mechanism utilized by S. aureus to block bacterial cell wall breakdown, limits the induction of pro-inflammatory signals required for optimal Th17 polarization. IL-10 deficiency in mice restores protective immunity to S. aureus infection, and adjuvancy with a staphylococcal peptidoglycan O-acetyltransferase mutant reduces IL-10, increases IL-1β, and promotes development of IL-17-dependent, Th cell-transferable protective immunity. Overall, our study suggests a mechanism whereby S. aureus modulates cytokines critical for induction of protective Th17 immunity.

人类通常不会对金黄色葡萄球菌再感染产生有效的免疫力。使用模仿人类感染的鼠模型，我们表明缺乏对金黄色葡萄球菌全身性再感染的保护性免疫力与强大的白介素10（IL-10）生产和受损的保护性Th17反应有关。在树突状细胞共培养试验中，金黄色葡萄球菌引发可促进强劲的T细胞增殖，但会限制Th细胞极化以及IL-1β和其他对Th1和Th17分化重要的细胞因子的产生。我们显示肽聚糖的O-乙酰化，金黄色葡萄球菌利用的机制阻止细菌细胞壁破裂，限制了最佳Th17极化所需的促炎信号的诱导。小鼠中IL-10缺乏症可恢复对金黄色葡萄球菌感染的保护性免疫力，并与葡萄球菌肽聚糖O-乙酰基转移酶突变体相邻可降低IL-10，增加IL-1β并促进IL-17依赖性，可Th细胞转移的保护性免疫。总的来说，我们的研究提出了一种机制，金黄色葡萄球菌可以调节诱导Th17保护性免疫至关重要的细胞因子。