Center for Microbial Pathogenesis, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
Present affiliation: Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
J Infect Dis. 2022 Jan 5;225(1):177-185. doi: 10.1093/infdis/jiab326.
Staphylococcus aureus infections are common throughout the lifespan, with recurrent infections occurring in nearly half of infected children. There is no licensed vaccine, underscoring the need to better understand how S. aureus evades protective immunity. Despite much study, the relative contributions of antibodies and T cells to protection against S. aureus infections in humans are not fully understood.
We prospectively quantified S. aureus-specific antibody levels by ELISA and T-cell responses by ELISpot in S. aureus-infected and healthy children.
S. aureus-specific antibody levels and T-cell responses increased with age in healthy children, suggesting a coordinated development of anti-staphylococcal immunity. Antibody levels against leukotoxin E (LukE) and Panton-Valentine leukocidin (LukS-PV), but not α-hemolysin (Hla), were higher in younger infected children, compared with healthy children; these differences disappeared in older children. We observed a striking impairment of global and S. aureus-specific T-cell function in children with invasive and noninvasive infection, suggesting that S. aureus-specific immune responses are dysregulated during childhood infection regardless of the infection phenotype.
These findings identify a potential mechanism by which S. aureus infection actively evades adaptive immune responses, thereby preventing the development of protective immunity and maintaining susceptibility to recurrent infection.
金黄色葡萄球菌感染在整个生命周期中很常见，近一半的感染儿童会发生反复感染。目前尚无获批的疫苗，这突显了人们需要更好地了解金黄色葡萄球菌如何逃避保护性免疫。尽管进行了大量研究，但人们对抗体和 T 细胞在人类预防金黄色葡萄球菌感染中的相对贡献仍不完全了解。
我们通过 ELISA 定量检测金黄色葡萄球菌感染和健康儿童的金黄色葡萄球菌特异性抗体水平，通过 ELISpot 检测 T 细胞反应。
健康儿童的金黄色葡萄球菌特异性抗体水平和 T 细胞反应随年龄增长而增加，表明抗金黄色葡萄球菌免疫呈协调发展。与健康儿童相比，感染后年龄较小的儿童针对白细胞毒素 E（LukE）和杀白细胞素 Panton-Valentine（LukS-PV）的抗体水平较高，而非α-溶血素（Hla）；这些差异在年龄较大的儿童中消失。我们观察到侵袭性和非侵袭性感染儿童的整体和金黄色葡萄球菌特异性 T 细胞功能明显受损，表明金黄色葡萄球菌特异性免疫反应在儿童感染期间失调，无论感染表型如何，均无法产生保护性免疫，从而保持对反复感染的易感性。
这些发现确定了金黄色葡萄球菌感染主动逃避适应性免疫反应的潜在机制，从而阻止了保护性免疫的发展并维持了对反复感染的易感性。
