Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands.
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Cell Rep Med. 2024 Sep 17;5(9):101734. doi: 10.1016/j.xcrm.2024.101734.
Staphylococcus aureus is a major human pathogen, yet the immune factors that protect against infection remain elusive. High titers of opsonic IgG antibodies, achieved in preclinical animal immunization studies, have consistently failed to provide protection in humans. Here, we investigate antibody responses to the conserved S. aureus surface glycan wall teichoic acid (WTA) and detect the presence of WTA-specific IgM and IgG antibodies in the plasma of healthy individuals. Functionally, WTA-specific IgM outperforms IgG in opsonophagocytic killing of S. aureus and protects against disseminated S. aureus bacteremia through passive immunization. In a clinical setting, patients with S. aureus bacteremia have significantly lower WTA-specific IgM but similar IgG levels compared to healthy controls. Importantly, low WTA-IgM levels correlate with disease mortality and impaired bacterial opsonization. Our findings may guide risk stratification of hospitalized patients and inform future design of antibody-based therapies and vaccines against serious S. aureus infection.
金黄色葡萄球菌是一种主要的人类病原体，但仍难以确定抵御感染的免疫因素。在临床前动物免疫研究中，高滴度的调理 IgG 抗体始终未能为人类提供保护。在这里，我们研究了对保守的金黄色葡萄球菌表面聚糖壁磷壁酸（WTA）的抗体反应，并在健康个体的血浆中检测到 WTA 特异性 IgM 和 IgG 抗体的存在。从功能上讲，WTA 特异性 IgM 在调理吞噬杀伤金黄色葡萄球菌方面优于 IgG，并通过被动免疫来预防金黄色葡萄球菌菌血症的扩散。在临床环境中，与健康对照组相比，金黄色葡萄球菌菌血症患者的 WTA 特异性 IgM 水平明显降低，但 IgG 水平相似。重要的是，低 WTA-IgM 水平与疾病死亡率和细菌调理作用受损相关。我们的研究结果可能有助于对住院患者进行风险分层，并为针对严重金黄色葡萄球菌感染的抗体治疗和疫苗的未来设计提供信息。
