Wawrzeniak Keith, Gaur Gauri, Sapi Eva, Senejani Alireza G
Department of Biology and Environmental Science, University of New Haven, West Haven, CT 06516, USA.
Antibiotics (Basel). 2020 May 25;9(5):275. doi: 10.3390/antibiotics9050275.
Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including , the causative agent of Lyme disease. The functional relationship between OMVs and host neuron homeostasis is not well understood. The objective of this study was to examine how OMVs impact the host cell environment. First, an in vitro model was established by co-culturing human BE2C neuroblastoma cells with B31. was able to invade BE2C cells within 24 h. Despite internalization, BE2C cell viability and levels of apoptosis remained unchanged, but resulted in dramatically increased production of MCP-1 and MCP-2 cytokines. Elevated secretion of MCP-1 has previously been associated with changes in oxidative stress. BE2C cell mitochondrial superoxides were reduced as early as 30 min after exposure to and OMVs. To rule out whether BE2C cell antioxidant response is the cause of decline in superoxides, superoxide dismutase 2 (SOD2) gene expression was assessed. SOD2 expression was reduced upon exposure to , suggesting that might be responsible for superoxide reduction. These results suggest that modulates cell antioxidant defense and immune system reaction in response to the bacterial infection. In summary, these results show that OMVs serve to directly counter superoxide production in BE2C neurons, thereby 'priming' the host environment to support colonization.
外膜囊泡(OMVs)是革兰氏阴性细菌释放的含有蛋白质和核酸的球形体,包括莱姆病的病原体。OMVs与宿主神经元稳态之间的功能关系尚未完全了解。本研究的目的是研究OMVs如何影响宿主细胞环境。首先,通过将人BE2C神经母细胞瘤细胞与B31共培养建立了体外模型。B31能够在24小时内侵入BE2C细胞。尽管发生了内化,但BE2C细胞活力和凋亡水平保持不变,但导致MCP-1和MCP-2细胞因子的产生显著增加。MCP-1分泌升高以前与氧化应激的变化有关。早在暴露于B31和OMVs后30分钟,BE2C细胞线粒体超氧化物就减少了。为了排除BE2C细胞抗氧化反应是否是超氧化物减少的原因,评估了超氧化物歧化酶2(SOD2)基因的表达。暴露于B31后,SOD2表达降低,这表明B31可能是超氧化物减少的原因。这些结果表明,B31在细菌感染时调节细胞抗氧化防御和免疫系统反应。总之,这些结果表明,B31的OMVs直接对抗BE2C神经元中超氧化物的产生,从而“启动”宿主环境以支持B31的定植。