Department of Medical Sciences, Section of Clinical Microbiology, Uppsala University, Uppsala, Sweden.
Department of Immunology, Genetics and Pathology-Biovis Platform, Uppsala University, Uppsala, Sweden.
BMC Microbiol. 2023 Apr 21;23(1):113. doi: 10.1186/s12866-023-02859-0.
Rickettsia helvetica, a spotted fever rickettsia, is transmitted to humans via ticks in Europe, North Africa, and Asia. The central nervous system is a crucial target for rickettsial diseases, which has been reported for 12 of the 31 species, of which R. helvetica is one. This study aimed, in an experimental model, to identify characteristics of R. helvetica infection in a mouse neuronal cell line, NSC-34.
NSC-34, a fusion cell line of mouse motor spinal cord neurons and neuroblastoma cells, was used as a model. Propagation of R. helvetica in neurons was confirmed. Short actin tails were shown at the polar end of the bacteria, which makes it likely that they can move intracellularly, and even spread between cells. Another protein, Sca4, which with the cell adhesion protein vinculin enables the passage of the cell membrane, was expressed during infection. No significant increase in TNFα levels was seen in the infected neurons, which is of interest because TNFα protects the host cell from infection-induced apoptotic death which is crucial for host cell survival. The bacteria were also shown to invade and grow in the cell nucleus of the neuron.
The findings suggest that a R. helvetica infection may be harmful to NSC-34 neurons under these in vitro conditions, but the full effects of the infection on the cell need to be studied further, also on human neurons, to also understand the possible significance of this infection in relation to pathogenetic mechanisms.
瑞士立克次体是一种斑疹热立克次体,通过欧洲、北非和亚洲的蜱传播给人类。中枢神经系统是立克次体病的一个关键靶点,在 31 种已知的立克次体物种中,有 12 种已报告存在中枢神经系统感染,其中包括瑞士立克次体。本研究旨在通过实验模型,鉴定瑞士立克次体感染小鼠神经元细胞系 NSC-34 的特征。
我们使用 NSC-34,一种小鼠运动脊髓神经元和神经母细胞瘤细胞的融合细胞系,作为模型。证实了瑞士立克次体在神经元中的繁殖。在细菌的极性端显示出短的肌动蛋白尾巴,这使得它们很可能能够在细胞内移动,甚至在细胞间传播。另一种蛋白 Sca4 在感染过程中表达,它与细胞黏附蛋白 vinculin 一起使细胞膜得以通过。在感染的神经元中未观察到 TNFα 水平的显著增加,这很有趣,因为 TNFα 可以保护宿主细胞免受感染诱导的凋亡死亡,这对于宿主细胞的存活至关重要。细菌还被证明可以入侵和在神经元的细胞核中生长。
这些发现表明,在这些体外条件下,瑞士立克次体感染可能对 NSC-34 神经元有害,但需要进一步研究感染对细胞的全部影响,包括对人类神经元的影响,以了解这种感染与发病机制相关的可能意义。