Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.
Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.
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对链球菌为链球菌表面蛋白的抗体促进病理炎症反应。
DOI：
10.1371/journal.ppat.1000149
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发表时间：
2008-09-12
期刊：
影响因子：
6.7
通讯作者：
Bjorck, Lars
中科院分区：
文献类型：
--
作者：
Kahn, Fredrik;Morgelin, Matthias;Shannon, Oonagh;Norrby-Teglund, Anna;Herwald, Heiko;Olin, Anders I.;Bjorck, Lars
由化脓性链球菌引起的链球菌中毒性休克综合征（STSS）是一种尽管经过现代重症监护但死亡率仍很高的临床疾病。STSS的一个关键特征是过多的血浆渗漏，导致低血容量性低血压、微循环障碍和多器官衰竭。以前的工作已经确定了STSS的毒力机制，其中S.化脓性链球菌与纤维蛋白原形成复合物，激活中性粒细胞释放肝素结合蛋白（HBP），这是血管渗漏的诱导物。在这里，我们报告了一个显着的个体间差异的反应M1蛋白诱导的HBP的释放，发现的差异是相关的IgG抗体针对M1蛋白的中心区域。为了引起大量的HBP释放，这些抗体需要成为M1蛋白-纤维蛋白原复合物的一部分。这些数据为细菌发病机制增加了一个新的方面，其中抗体通过促进病理性炎症反应而导致疾病的严重程度。 化脓性链球菌，也称为A组链球菌，是一种常见的细菌病原体，主要引起相当无害的感染，如咽炎（“链球菌性咽喉炎”）和脓疱病（一种浅表皮肤感染）。然而，有时这些细菌会引起严重的侵入性感染，感染医学中最可怕的情况之一是链球菌中毒性休克综合征（STSS）。在STSS中，尽管有现代化的重症监护和S。化脓菌对青霉素敏感。为什么有些人发展这种严重的情况，而其他人没有仍然没有完全理解。通常的教条是，针对病原微生物的抗体具有保护作用，但在这项工作中，我们表明某些抗体实际上会增加更严重疾病的风险。这些信息表明，这些抗体可用作治疗靶点，结果也可能有助于识别易于发展STSS的个体。
Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein–induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein–fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response. Streptococcus pyogenes, also known as group A streptococcus, is a common bacterial pathogen mostly causing rather harmless infections such as pharyngitis (“strep throat”) and impetigo (a superficial skin infection). However, sometimes these bacteria give rise to severe invasive infections, and one of the most feared conditions in infection medicine is streptococcal toxic shock syndrome (STSS). In STSS, the mortality remains high despite modern intensive care and the fact that S. pyogenes is susceptible to penicillin. Why some people develop this serious condition and others not is still not fully understood. The common dogma is that antibodies against a pathogenic microorganism are protective, but in this work we show that certain antibodies actually increase the risk for a more severe disease. This information suggests that these antibodies could be used as therapeutic targets, and the results may also facilitate the identification of individuals prone to developing STSS.
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影响因子：
6.4
作者：
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