Glycan-specific IgM is critical for human immunity to Staphylococcus aureus

IF 11.7 1区 医学 Q1 CELL BIOLOGY Cell Reports Medicine Pub Date : 2024-09-17 DOI:10.1016/j.xcrm.2024.101734
Astrid Hendriks, Priscilla F. Kerkman, Meri R.J. Varkila, Jelle L.G. Haitsma Mulier, Sara Ali, Thijs ten Doesschate, Thomas W. van der Vaart, Carla J.C. de Haas, Piet C. Aerts, Olaf L. Cremer, Marc J.M. Bonten, Victor Nizet, George Y. Liu, Jeroen D.C. Codée, Suzan H.M. Rooijakkers, Jos A.G. van Strijp, Nina M. van Sorge
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Abstract

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.

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糖蛋白特异性 IgM 对人类免疫金黄色葡萄球菌至关重要
金黄色葡萄球菌是一种主要的人类病原体,但保护人体免受感染的免疫因子仍然难以捉摸。临床前动物免疫研究中获得的高滴度 opsonic IgG 抗体一直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茶色酸(WTA)的抗体反应,并检测了健康人血浆中 WTA 特异性 IgM 和 IgG 抗体的存在。从功能上讲,WTA 特异性 IgM 在杀死金黄色葡萄球菌的嗜蛋白吞噬功能上优于 IgG,并能通过被动免疫防止传播性金黄色葡萄球菌菌血症。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 水平明显较低,但 IgG 水平相似。重要的是,WTA-IgM 水平低与疾病死亡率和细菌溶菌功能受损有关。我们的研究结果可为住院患者的风险分层提供指导,并为未来设计抗严重金黄色葡萄球菌感染的抗体疗法和疫苗提供参考。
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来源期刊
Cell Reports Medicine
Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
15.00
自引率
1.40%
发文量
231
审稿时长
40 days
期刊介绍: Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.
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