Ochel Anja, Rohde Manfred, Chhatwal Gursharan S, Talay Susanne R
Department of Medical Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
J Innate Immun. 2014;6(5):585-96. doi: 10.1159/000358085. Epub 2014 Jan 31.
Serotype M1 Streptococcus pyogenes is a major human pathogen associated with severe invasive diseases causing high morbidity and mortality. In a substantial number of cases, invasive disease develops in previously healthy individuals with no obvious port of entry. This has led to the hypothesis that the source of streptococci in these cases is a transient bacteraemia. This study focuses on the analysis of interaction of tissue-invasive serotype M1 S. pyogenes with human endothelial cells (EC) of the vascular system. We identify the M1 surface protein of S. pyogenes as the EC invasin which is recognised by polarized human blood EC, thereby triggering rapid, phagocytosis-like uptake of streptococci into polarized EC layers. Upon internalization, the M1 S. pyogenes serotype is incorporated into phagosomes which traffic via the endosomal/lysosomal pathway. However, some of the streptococci successfully evade this innate killing process and hereby mediate their escape into the cytoplasm of the host cell. The results of this study demonstrate that blood EC possess an efficient uptake mechanism for serotype M1 S. pyogenes. Despite efficient phagocytosis, streptococcal survival within EC constitutes one potential mechanism which favours intracellular persistence and thus facilitates continuous infection and dissemination from the primary side of infection into deep tissue.
M1 型化脓性链球菌是一种主要的人类病原体，与严重的侵袭性疾病相关，可导致高发病率和死亡率。在大量病例中，侵袭性疾病发生在先前健康且无明显侵入途径的个体中。这引发了一种假说，即在这些病例中，链球菌的来源是短暂菌血症。本研究聚焦于分析组织侵袭性 M1 型化脓性链球菌与血管系统的人内皮细胞（EC）之间的相互作用。我们确定化脓性链球菌的 M1 表面蛋白为 EC 侵袭素，其被极化的人血 EC 识别，从而触发链球菌快速、类似吞噬作用的摄取进入极化的 EC 层。内化后，M1 型化脓性链球菌血清型被纳入通过内体/溶酶体途径运输的吞噬体中。然而，一些链球菌成功逃避了这种先天性杀伤过程，从而介导它们逃逸到宿主细胞的细胞质中。本研究结果表明，血液 EC 对 M1 型化脓性链球菌具有高效的摄取机制。尽管吞噬作用有效，但 EC 内的链球菌存活构成了一种潜在机制，有利于细胞内持续存在，从而促进从感染原发部位持续感染和扩散到深部组织。
