Dinis Márcia, Plainvert Céline, Kovarik Pavel, Longo Magalie, Fouet Agnès, Poyart Claire
INSERM U 1016, Institut Cochin, Unité FRM "Barrières et Pathogènes", Paris, France; CNRS UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
INSERM U 1016, Institut Cochin, Unité FRM "Barrières et Pathogènes", Paris, France; CNRS UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre National de Référence des Streptocoques, Paris, France; Hôpitaux Universitaires Paris Centre, Site Cochin, Assistance Publique Hôpitaux de Paris, Paris, France.
PLoS One. 2014 Jul 3;9(7):e101464. doi: 10.1371/journal.pone.0101464. eCollection 2014.
Group A Streptococcus (GAS) infections remain a significant health care problem due to high morbidity and mortality associated with GAS diseases, along with their increasing worldwide prevalence. Macrophages play a key role in the control and clearance of GAS infections. Moreover, pro-inflammatory cytokines production and GAS persistence and invasion are related. In this study we investigated the correlation between the GAS clinical isolates genotypes, their known clinical history, and their ability to modulate innate immune response. We constituted a collection of 40 independent GAS isolates representative of the emm types currently prevalent in France and responsible for invasive (57.5%) and non-invasive (42.5%) clinical manifestations. We tested phagocytosis and survival in mouse bone marrow-derived macrophages and quantified the pro-inflammatory mediators (IL-6, TNF-α) and type I interferon (INF-β) production. Invasive emm89 isolates were more phagocytosed than their non-invasive counterparts, and emm89 isolates more than the other isolates. Regarding the survival, differences were observed depending on the isolate emm type, but not between invasive and non-invasive isolates within the same emm type. The level of inflammatory mediators produced was also emm type-dependent and mostly invasiveness status independent. Isolates of the emm1 type were able to induce the highest levels of both pro-inflammatory cytokines, whereas emm89 isolates induced the earliest production of IFN-β. Finally, even within emm types, there was a variability of the innate immune responses induced, but survival and inflammatory mediator production were not linked.
由于与A组链球菌（GAS）疾病相关的高发病率和死亡率，以及其在全球范围内的患病率不断上升，GAS感染仍然是一个重大的医疗保健问题。巨噬细胞在GAS感染的控制和清除中起关键作用。此外，促炎细胞因子的产生与GAS的持续存在和侵袭有关。在本研究中，我们调查了GAS临床分离株的基因型、其已知临床病史与其调节先天免疫反应能力之间的相关性。我们收集了40株独立的GAS分离株，它们代表了目前在法国流行的emm型，并导致侵袭性（57.5%）和非侵袭性（42.5%）临床表现。我们测试了它们在小鼠骨髓来源巨噬细胞中的吞噬作用和存活率，并量化了促炎介质（IL-6、TNF-α）和I型干扰素（INF-β）的产生。侵袭性emm89分离株比非侵袭性对应株更容易被吞噬，并且emm89分离株比其他分离株更容易被吞噬。关于存活率，根据分离株的emm型观察到差异，但在同一emm型内的侵袭性和非侵袭性分离株之间没有差异。产生的炎症介质水平也依赖于emm型，并且大多与侵袭状态无关。emm1型分离株能够诱导产生最高水平的两种促炎细胞因子，而emm89分离株诱导IFN-β的产生最早。最后，即使在emm型内，诱导的先天免疫反应也存在变异性，但存活率和炎症介质产生之间没有关联。
