Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Sweden.
J Infect Dis. 2013 Dec 15;208(12):2025-35. doi: 10.1093/infdis/jit359. Epub 2013 Jul 30.
Group B streptococcus (GBS) is a leading neonatal pathogen and a growing cause of invasive disease in the elderly, with clinical manifestations such as pneumonia and sepsis. Despite its clinical importance, little is known about innate immunity against GBS in humans. Here, we analyze the role of human group IIA secreted phospholipase A2 (sPLA2-IIA), a bactericidal enzyme induced during acute inflammation, in innate immunity against GBS. We show that clinical GBS isolates are highly sensitive to killing by sPLA2-IIA but not by human antimicrobial peptides. Using transgenic mice that express human sPLA2-IIA, we demonstrate that this enzyme is crucial for host protection against systemic infection and lung challenge by GBS. We found that acute sera from humans diagnosed with invasive GBS disease contain increased levels of sPLA2-IIA compared with normal sera from healthy individuals, indicating that GBS induces an sPLA2-IIA response in blood during human infection. We demonstrate that clinically relevant GBS strains are rapidly killed in these acute sera. We also demonstrate that the bactericidal effect is entirely due to sPLA2-IIA, showing that sPLA2-IIA might represent an important component of humoral innate immunity against GBS. Our data provide experimental and clinical evidence that sPLA2-IIA protects humans against GBS infections.
B 群链球菌（GBS）是一种主要的新生儿病原体，也是老年人侵袭性疾病（如肺炎和败血症）日益增多的病因。尽管其具有重要的临床意义，但人们对人类针对 GBS 的先天免疫知之甚少。在这里，我们分析了人类 IIA 组分泌型磷脂酶 A2（sPLA2-IIA）在针对 GBS 的先天免疫中的作用，sPLA2-IIA 是一种在急性炎症期间诱导产生的杀菌酶。我们表明，临床 GBS 分离株对 sPLA2-IIA 的杀伤高度敏感，但对人类抗菌肽不敏感。使用表达人 sPLA2-IIA 的转基因小鼠，我们证明该酶对于宿主免受 GBS 全身性感染和肺部攻击至关重要。我们发现，与健康个体的正常血清相比，诊断为侵袭性 GBS 疾病的人类急性血清中 sPLA2-IIA 水平升高，表明 GBS 在人类感染期间在血液中诱导 sPLA2-IIA 反应。我们表明，临床相关的 GBS 菌株在这些急性血清中迅速被杀灭。我们还表明，杀菌作用完全归因于 sPLA2-IIA，表明 sPLA2-IIA 可能是针对 GBS 的体液先天免疫的重要组成部分。我们的数据提供了实验和临床证据，表明 sPLA2-IIA 可保护人类免受 GBS 感染。
