Siemens Nikolai, Oehmcke-Hecht Sonja, Hoßmann Jörn, Skorka Sebastian B, Nijhuis Roel H T, Ruppen Corinne, Skrede Steinar, Rohde Manfred, Schultz Daniel, Lalk Michael, Itzek Andreas, Pieper Dietmar H, van den Bout Christiaan J, Claas Eric C J, Kuijper Ed J, Mauritz Robert, Sendi Parham, Wunderink Herman F, Norrby-Teglund Anna
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden,
Center for Functional Genomics of Microbes, Department of Molecular Genetics and Infection Biology, University of Greifswald, Greifswald, Germany,
J Innate Immun. 2020;12(4):291-303. doi: 10.1159/000504002. Epub 2019 Nov 19.
A prominent feature of severe streptococcal infections is the profound inflammatory response that contributes to systemic toxicity. In sepsis the dysregulated host response involves both immunological and nonimmunological pathways. Here, we report a fatal case of an immunocompetent healthy female presenting with toxic shock and purpura fulminans caused by group B streptococcus (GBS; serotype III, CC19). The strain (LUMC16) was pigmented and hyperhemolytic. Stimulation of human primary cells with hyperhemolytic LUMC16 and STSS/NF-HH strains and pigment toxin resulted in a release of proinflammatory mediators, including tumor necrosis factor, interleukin (IL)-1β, and IL-6. In addition, LUMC16 induced blood clotting and showed factor XII activity on its surface, which was linked to the presence of the pigment. The expression of pigment was not linked to a mutation within the CovR/S region. In conclusion, our study shows that the hemolytic lipid toxin contributes to the ability of GBS to cause systemic hyperinflammation and interferes with the coagulation system.
严重链球菌感染的一个显著特征是导致全身毒性的强烈炎症反应。在脓毒症中，失调的宿主反应涉及免疫和非免疫途径。在此，我们报告一例由B族链球菌（GBS；血清型III，CC19）引起的中毒性休克和暴发性紫癜的免疫功能正常健康女性死亡病例。该菌株（LUMC16）有色素沉着且溶血活性增强。用溶血活性增强的LUMC16和STSS/NF-HH菌株以及色素毒素刺激人原代细胞会导致促炎介质的释放，包括肿瘤坏死因子、白细胞介素（IL）-1β和IL-6。此外，LUMC16诱导血液凝固并在其表面显示出因子XII活性，这与色素的存在有关。色素的表达与CovR/S区域内的突变无关。总之，我们的研究表明溶血脂质毒素有助于GBS引起全身过度炎症并干扰凝血系统。
