The mechanisms that mediate durable protection against Staphylococcus aureus skin reinfections are unclear, as recurrences are common despite high antibody titers and memory T cells. Here, we developed a mouse model of S. aureus skin reinfection to investigate protective memory responses. In contrast with WT mice, IL-1β–deficient mice exhibited poor neutrophil recruitment and bacterial clearance during primary infection that was rescued during secondary S. aureus challenge. The γδ T cells from skin-draining LNs utilized compensatory T cell–intrinsic TLR2/MyD88 signaling to mediate rescue by trafficking and producing TNF and IFN-γ, which restored neutrophil recruitment and promoted bacterial clearance. RNA-sequencing (RNA-seq) of the LNs revealed a clonotypic S. aureus–induced γδ T cell expansion with a complementarity-determining region 3 (CDR3) aa sequence identical to that of invariant Vγ5⁺ dendritic epidermal T cells. However, this T cell receptor γ (TRG) aa sequence of the dominant CDR3 sequence was generated from multiple gene rearrangements of TRGV5 and TRGV6, indicating clonotypic expansion. TNF- and IFN-γ–producing γδ T cells were also expanded in peripheral blood of IRAK4-deficient humans no longer predisposed to S. aureus skin infections. Thus, clonally expanded γδ T cells represent a mechanism for long-lasting immunity against recurrent S. aureus skin infections.

中文翻译：

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克隆扩增的 γδ T 细胞可预防金黄色葡萄球菌皮肤再感染


介导针对金黄色葡萄球菌皮肤再感染的持久保护的机制尚不清楚，因为尽管抗体滴度和记忆 T 细胞很高，但复发很常见。在这里，我们开发了S的小鼠模型。金黄色葡萄球菌皮肤再感染，以研究保护性记忆反应。与 WT 小鼠相比，IL-1β 缺陷小鼠在初次感染期间表现出较差的中性粒细胞募集和细菌清除能力，但在继发性S感染期间得到了挽救。金黄色葡萄球菌挑战。来自皮肤引流淋巴结的 γδ T 细胞利用补偿性 T 细胞固有的 TLR2/MyD88 信号传导，通过运输和产生 TNF 和 IFN-γ 来介导救援，从而恢复中性粒细胞募集并促进细菌清除。 LN 的 RNA 测序 (RNA-seq) 揭示了克隆型S 。金黄色葡萄球菌诱导 γδ T 细胞扩增，其互补决定区 3 (CDR3) aa 序列与不变的 Vγ5 ⁺树突状表皮 T 细胞相同。然而，显性 CDR3 序列的 T 细胞受体 γ ( TRG ) 序列是由TRGV5和TRGV6的多个基因重排产生的，表明克隆型扩展。产生 TNF 和 IFN-γ 的 γδ T 细胞也在缺乏 IRAK4 且不再易感染金黄色葡萄球菌的人的外周血中扩增。金黄色葡萄球菌皮肤感染。因此，克隆扩增的 γδ T 细胞代表了针对复发性金黄色葡萄球菌的长期免疫机制。金黄色葡萄球菌皮肤感染。