Bacterial superantigens (SAgs) cause Vβ-dependent T-cell proliferation leading to immune dysregulation associated with the pathogenesis of life-threatening infections such as toxic shock syndrome, and necrotizing pneumonia. Previously, we demonstrated that staphylococcal enterotoxin-like toxin X (SElX) from Staphylococcus aureus is a classical superantigen that exhibits T-cell activation in a Vβ-specific manner, and contributes to the pathogenesis of necrotizing pneumonia. Here, we discovered that SElX can also bind to neutrophils from human and other mammalian species and disrupt IgG-mediated phagocytosis. Site-directed mutagenesis of the conserved sialic acid-binding motif of SElX abolished neutrophil binding and phagocytic killing, and revealed multiple glycosylated neutrophil receptors for SElX binding. Furthermore, the neutrophil binding-deficient mutant of SElX retained its capacity for T-cell activation demonstrating that SElX exhibits mechanistically independent activities on distinct cell populations associated with acquired and innate immunity, respectively. Finally, we demonstrated that the neutrophil-binding activity rather than superantigenicity is responsible for the SElX-dependent virulence observed in a necrotizing pneumonia rabbit model of infection. Taken together, we report the first example of a SAg, that can manipulate both the innate and adaptive arms of the human immune system during S. aureus pathogenesis.

细菌超抗原（SAg）导致Vβ依赖性T细胞增殖，导致免疫失调，与威胁生命的感染（如中毒性休克综合症和坏死性肺炎）的发病机理相关。以前，我们证明了来自金黄色葡萄球菌的葡萄球菌肠毒素样毒素X（SElX）是经典的超抗原，其以Vβ特异性方式表现出T细胞活化，并有助于坏死性肺炎的发病机理。在这里，我们发现SElX还可以与人类和其他哺乳动物物种的嗜中性白细胞结合并破坏IgG介导的吞噬作用。SElX的保守唾液酸结合基序的定点诱变消除了嗜中性粒细胞结合和吞噬杀伤，并揭示了多个糖基化嗜中性粒细胞受体的SElX结合。此外，SElX的嗜中性粒细胞结合缺陷型突变体保留了其T细胞活化的能力，这表明SElX在与获得性免疫和先天免疫相关的不同细胞群体上分别表现出机械独立的活性。最后，我们证明嗜中性粒细胞结合活性而不是超抗原性是导致在感染性坏死性肺炎兔模型中观察到的SElX依赖性毒力的原因。综上所述，我们报告了SAg的第一个例子，它可以在免疫过程中操纵人类免疫系统的先天性和适应性臂小号。金黄色葡萄球菌的发病机理。