Institute of Biology, Leiden University, Leiden, Netherlands.
Front Immunol. 2021 May 11;12:618569. doi: 10.3389/fimmu.2021.618569. eCollection 2021.
Glucocorticoids are effective drugs for treating immune-related diseases, but prolonged therapy is associated with an increased risk of various infectious diseases, including tuberculosis. In this study, we have used a larval zebrafish model for tuberculosis, based on () infection, to study the effect of glucocorticoids. Our results show that the synthetic glucocorticoid beclomethasone increases the bacterial burden and the dissemination of a systemic infection. The exacerbated infection was associated with a decreased phagocytic activity of macrophages, higher percentages of extracellular bacteria, and a reduced rate of infected cell death, whereas the bactericidal capacity of the macrophages was not affected. The inhibited phagocytic capacity of macrophages was associated with suppression of the transcription of genes involved in phagocytosis in these cells. The decreased bacterial phagocytosis by macrophages was not specific for , since it was also observed upon infection with Typhimurium. In conclusion, our results show that glucocorticoids inhibit the phagocytic activity of macrophages, which may increase the severity of bacterial infections like tuberculosis.
糖皮质激素是治疗免疫相关疾病的有效药物，但长期治疗会增加各种传染病的风险，包括结核病。在这项研究中，我们使用了一种基于 ()感染的结核性幼鱼斑马鱼模型来研究糖皮质激素的作用。我们的结果表明，合成糖皮质激素倍氯米松增加了细菌负荷和全身性感染的传播。感染加重与巨噬细胞吞噬活性降低、胞外细菌百分比升高以及感染细胞死亡率降低有关，而巨噬细胞的杀菌能力不受影响。巨噬细胞吞噬能力的抑制与这些细胞中参与吞噬作用的基因转录抑制有关。巨噬细胞对细菌的吞噬作用降低并非仅限于 ，因为在感染 鼠伤寒沙门氏菌时也观察到了这种情况。总之，我们的结果表明，糖皮质激素抑制巨噬细胞的吞噬活性，这可能会增加像结核病这样的细菌感染的严重程度。
