Université de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.
Département Hospitalo-Universitaire Risk & Pregnancy, Port Royal Maternity, Paris, France.
J Clin Invest. 2021 Feb 15;131(4). doi: 10.1172/JCI130746.
Group A Streptococcus (GAS), a Gram-positive human-specific pathogen, yields 517,000 deaths annually worldwide, including 163,000 due to invasive infections and among them puerperal fever. Before efficient prophylactic measures were introduced, the mortality rate for mothers during childbirth was approximately 10%; puerperal fever still accounts for over 75,000 maternal deaths annually. Yet, little is known regarding the factors and mechanisms of GAS invasion and establishment in postpartum infection. We characterized the early steps of infection in an ex vivo infection model of the human decidua, the puerperal fever portal of entry. Coordinate analysis of GAS behavior and the immune response led us to demonstrate that (a) GAS growth was stimulated by tissue products; (b) GAS invaded tissue and killed approximately 50% of host cells within 2 hours, and these processes required SpeB protease and streptolysin O (SLO) activities, respectively; and (c) GAS impaired the tissue immune response. Immune impairment occurred both at the RNA level, with only partial induction of the innate immune response, and protein level, in an SLO- and SpeB-dependent manner. Our study indicates that efficient GAS invasion of the decidua and the restricted host immune response favored its propensity to develop rapid invasive infections in a gynecological-obstetrical context.
A 组链球菌（GAS）是一种革兰氏阳性的人类病原体，每年在全球造成 51.7 万人死亡，其中包括 16.3 万人因侵袭性感染而死亡，其中包括产褥热。在引入有效的预防措施之前，产妇在分娩时的死亡率约为 10%；产褥热每年仍导致超过 7.5 万名母亲死亡。然而，对于 GAS 侵袭和在产后感染中定植的因素和机制，人们知之甚少。我们在人类蜕膜的体外感染模型中描述了感染的早期步骤，这是产褥热的感染门户。GAS 行为和免疫反应的协调分析使我们能够证明：（a）组织产物刺激 GAS 生长；（b）GAS 在 2 小时内侵入组织并杀死大约 50%的宿主细胞，这些过程分别需要 SpeB 蛋白酶和链球菌溶血素 O（SLO）的活性；（c）GAS 损害了组织的免疫反应。免疫损伤既发生在 RNA 水平，固有免疫反应的诱导不完全，也发生在蛋白质水平，这两种情况都依赖于 SLO 和 SpeB。我们的研究表明，GAS 有效地侵袭蜕膜，宿主的免疫反应受到限制，这有利于其在妇科产科环境中迅速发展侵袭性感染。
