Division of Infection Medicine, Department of Clinical Sciences, Lund University, SE-22184, Lund, Sweden.
Anaerobe. 2022 Jun;75:102584. doi: 10.1016/j.anaerobe.2022.102584. Epub 2022 May 8.
Gram-positive anaerobic cocci (GPAC) are often regarded as harmless commensals associated with skin and mucosal surfaces. Investigations regarding these bacterial species often concern clinical case reports. In immunocompromised individuals, in the presence of comorbidities, such as diabetes or due to breach of skin barriers, the GPAC can cause infections. Nonetheless, information on the direct impact of these bacteria on blood-derived immune cells remains sparse.
Heat-inactivated GPAC strains (Finegoldia magna, Peptoniphilus harei, Parvimonas micra and Anaerococcus spp.) were incubated with whole blood from healthy human donors for 15 min or 4 h. Following the incubation, plasma samples were collected and analysed by ELISA for secretion of heparin-binding protein (HBP), myeloperoxidase (MPO), calprotectin (S100A8/S100A9; MRP-8/MRP-14) and TNFα as markers for immune cell activation.
The direct interaction of GPAC with whole blood demonstrated a significant effect on the immune response. Incubation of the bacterial strains with blood triggered rapid secretion of sepsis markers HBP and calprotectin, as well as the pro-inflammatory cytokine TNFα. Due to lack of MPO secretion at the early time point, it was hypothesised that the early HBP originated from the neutrophil secretory vesicles. Trypsin-treatment of the bacteria slightly reduced the HBP release, suggesting an involvement of bacterial surface proteins.
The findings suggest that GPAC species isolated from blood might pose an underestimated threat to the host. Further research concerning anaerobic cocci in direct interaction with the human host is therefore needed and justified.
革兰阳性厌氧球菌（GPAC）通常被认为是与皮肤和黏膜表面相关的无害共生菌。关于这些细菌的研究通常涉及临床病例报告。在免疫功能低下的个体中，存在合并症（如糖尿病）或由于皮肤屏障受损，GPAC 可引起感染。然而，这些细菌对血液来源的免疫细胞的直接影响的信息仍然很少。
将热灭活的 GPAC 菌株（大芬戈尔德菌、毛螺菌属、微小消化链球菌和厌氧球菌属）与健康人类供体的全血孵育 15 分钟或 4 小时。孵育后，收集血浆样本并通过 ELISA 分析肝素结合蛋白（HBP）、髓过氧化物酶（MPO）、钙卫蛋白（S100A8/S100A9；MRP-8/MRP-14）和 TNFα 的分泌，作为免疫细胞激活的标志物。
GPAC 与全血的直接相互作用对免疫反应有显著影响。细菌株与血液孵育会触发脓毒症标志物 HBP 和钙卫蛋白以及促炎细胞因子 TNFα 的快速分泌。由于在早期时间点缺乏 MPO 的分泌，因此假设早期 HBP 源自中性粒细胞的分泌小泡。对细菌进行胰蛋白酶处理可轻微减少 HBP 的释放，表明细菌表面蛋白的参与。
这些发现表明，从血液中分离出的 GPAC 物种可能对宿主构成被低估的威胁。因此，需要并合理地进行关于与人类宿主直接相互作用的厌氧球菌的进一步研究。
