Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Science, Nankai University, Tianjin 300071, P. R. China.
FEMS Yeast Res. 2020 Jun 1;20(4). doi: 10.1093/femsyr/foz081.
Candida albicans is a common pathogenic fungus with high mortality in immunocompromised patients. However, the mechanism by which C. albicans invades host epithelial cells and causes serious tissue damage remains to be further investigated. In this study, we established the C. albicans-293T renal epithelial cell interaction model to investigate the mechanism of epithelial infection by this pathogen. It was found that C. albicans infection causes severe cell death and reactive oxygen species (ROS) accumulation in epithelial cells. Further investigations revealed that C. albicans infection might up-regulate expression of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX), inhibit the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and suppress the p38-Nrf2-heme oxygenase-1 (HO-1) pathway which plays an important role in the elimination of intracellular ROS. Furthermore, epithelial cell death caused by the fungal infection could be strikingly alleviated by addition of the antioxidant agent glutathione, indicating the critical role of ROS accumulation in cell death caused by the fungus. This study revealed that disturbance of the redox homeostasis system and ROS accumulation in epithelial cells is involved in cell death caused by C. albicans infection, which sheds light on the application of antioxidants in the suppression of tissue damage caused by fungal infection.
白色念珠菌是一种常见的致病性真菌，在免疫功能低下的患者中死亡率很高。然而，白色念珠菌侵袭宿主上皮细胞并导致严重组织损伤的机制仍需进一步研究。在本研究中，我们建立了白色念珠菌-293T 肾上皮细胞相互作用模型，以研究该病原体引起上皮感染的机制。结果发现，白色念珠菌感染导致上皮细胞严重死亡和活性氧（ROS）积累。进一步的研究表明，白色念珠菌感染可能上调烟酰胺腺嘌呤二核苷酸磷酸（NAPDH）氧化酶（NOX）的表达，抑制抗氧化酶超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性，并抑制 p38-Nrf2-血红素加氧酶-1（HO-1）通路，该通路在清除细胞内 ROS 中起重要作用。此外，抗氧化剂谷胱甘肽的添加可显著减轻真菌感染引起的上皮细胞死亡，表明 ROS 积累在真菌引起的细胞死亡中起关键作用。本研究揭示了上皮细胞氧化还原平衡系统紊乱和 ROS 积累参与了白色念珠菌感染引起的细胞死亡，这为抗氧化剂在抑制真菌感染引起的组织损伤中的应用提供了思路。
