PDF(Pubmed)
Abstract：
The human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain specific or more broadly protective. Here, we quantified the opsonic-antibody response following invasive S. pyogenes infection. Four patients with S. pyogenes bacteremia between 2018 and 2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute- and convalescent-phase sera were obtained, and the S. pyogenes isolates were genome sequenced (emm118, emm85, and two emm1 isolates). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in response to infection. Antibody binding increased modestly against the infecting isolate and across emm types in convalescent- compared to acute-phase sera for all patients. For two patients, phagocytosis increased in convalescent-phase serum both for the infecting isolate and across types. The increase was only across types for one patient, and one had no improvement. No correlation to the clinical outcomes was observed. Invasive S. pyogenes infections result in a modestly increased antibody binding with differential opsonic capacity, both nonfunctional binding and broadly opsonic binding across types. These findings question the dogma that an invasive infection should lead to a strong type-specific antibody increase rather than a more modest but broadly reactive response, as seen in these patients. Furthermore, our results indicate that an increase in antibody titers might not be indicative of an opsonic response and highlight the importance of evaluating antibody function in S. pyogenes infections. IMPORTANCE The bacterium Streptococcus pyogenes is a common cause of both mild and severe human diseases resulting in substantial morbidity and mortality each year. No vaccines are available, and our understanding of the antibody response to this human pathogen is still incomplete. Here, we carefully analyzed the opsonic antibody response following invasive infection in four patients. Unexpectedly, the patients did not always generate opsonic antibodies against the specific infecting strain. Instead, we found that some patients could generate cross-opsonic antibodies, leading to phagocytosis of bacteria across strains. The emergence of cross-opsonic antibodies is likely important for long-term immunity against S. pyogenes. Our findings question the dogma that mostly strain-specific immunity is developed after infection and add to our overall understanding of how immunity to S. pyogenes can evolve.
摘要：
人类病原体化脓性链球菌引起大量发病率和死亡率。目前尚不清楚这种病原体感染后产生的抗体是否是调理性的，以及它们是否是菌株特异性的或更广泛的保护性的。这里,我们定量了侵袭性化脓性链球菌感染后的调理抗体反应。2018年至2020年在隆德的斯科恩大学医院治疗的四名化脓性链球菌菌血症患者，瑞典,被前瞻性登记。获得了急性期和恢复期血清，和化脓性链球菌分离株进行基因组测序（emm118，emm85和两个emm1分离株）。定量抗体结合和吞噬作用测定用于评估响应于感染的分离物依赖性调理抗体功能。与所有患者的急性期血清相比，恢复期中针对感染分离株和跨emm类型的抗体结合适度增加。对两个病人来说,感染分离株和跨类型的恢复期血清中的吞噬作用均增加。仅针对一名患者的类型增加，一个没有改善。未观察到与临床结果相关。浸润性化脓性链球菌感染导致适度增加的抗体结合差异调理能力。跨类型的无功能结合和广泛的调理结合。这些发现质疑一种教条，即侵入性感染应该导致强烈的类型特异性抗体增加，而不是更温和但广泛的反应性反应。从这些病人身上看到的。此外，我们的结果表明,抗体滴度的增加可能并不表示有调理反应,并突出了在化脓性链球菌感染中评估抗体功能的重要性.重要性化脓性链球菌是导致每年大量发病率和死亡率的轻度和严重人类疾病的常见原因。没有疫苗可用，我们对这种人类病原体的抗体反应的理解仍然不完整。这里,我们仔细分析了4例患者侵袭性感染后的调理性抗体反应.出乎意料的是,患者并不总是产生针对特定感染菌株的调理抗体.相反，我们发现一些患者可以产生交叉调理抗体，导致跨菌株的细菌吞噬。交叉调理抗体的出现对于针对化脓性链球菌的长期免疫可能是重要的。我们的发现质疑主要是菌株特异性免疫是在感染后发展起来的教条，并增加了我们对化脓性链球菌免疫如何进化的整体理解。
