Jiangsu Key Laboratory of Molecular Biology for Skin, Institute of Dermatology, Diseases and STIs, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, 210042, People's Republic of China.
Department of Dermatology, First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, 330001, People's Republic of China.
Mycopathologia. 2021 Jun;186(3):341-354. doi: 10.1007/s11046-021-00538-0. Epub 2021 Jun 4.
Aspergillus fumigatu (A. fumigatus) is one of the most common important fungal pathogens that cause life-threatening infectious disease in immunocompromised individuals. However, the host immune response against this pathogenic mold is not fully understood. MicroRNAs (miRNAs) play essential roles in regulating innate immunity. Thus, we investigated the function of miR-146a in inflammatory responses in macrophages after A. fumigatus stimulation in this study. We found that TNF-α and IL-6 were increased in THP-1 macrophage-like cells treated with A. fumigatus at both the mRNA and protein levels. The interaction between THP-1 macrophage-like cells and A. fumigatus resulted in a long-lasting increase in miR-146a expression dependent on p38 MAPK and NF-κB signaling. In A. fumigatus-challenged THP-1 macrophage-like cells, overexpression of miR-146a by miR-146a mimics decreased TNF-α and IL-6 production, whereas downregulation of miR-146a by anti-miR-146a significantly enhanced the level of TNF-α and IL-6. Our study demonstrates that the crosstalk between miR-146a and the inflammation-regulating p38 MAPK and NF-κB pathways might be a fine-tuning mechanism in the modulation of the inflammatory response in macrophages infected with A. fumigatus. Our findings illuminate the crucial role of miR-146a in the pathogenesis of human diseases associated with A. fumigatus infection.
烟曲霉（A. fumigatus）是最常见的重要真菌病原体之一，可导致免疫功能低下个体发生危及生命的感染性疾病。然而，宿主对这种致病霉菌的免疫反应尚未完全阐明。微小 RNA（miRNA）在调节先天免疫中发挥重要作用。因此，我们在这项研究中研究了 miR-146a 在烟曲霉刺激后巨噬细胞炎症反应中的作用。我们发现，烟曲霉处理的 THP-1 巨噬细胞样细胞中 TNF-α和 IL-6 的 mRNA 和蛋白水平均升高。THP-1 巨噬细胞样细胞与烟曲霉的相互作用导致 miR-146a 的表达持续增加，这依赖于 p38 MAPK 和 NF-κB 信号通路。在烟曲霉挑战的 THP-1 巨噬细胞样细胞中，miR-146a 模拟物过表达降低了 TNF-α和 IL-6 的产生，而 anti-miR-146a 下调则显著增强了 TNF-α和 IL-6 的水平。我们的研究表明，miR-146a 与炎症调节的 p38 MAPK 和 NF-κB 通路之间的串扰可能是调节烟曲霉感染的巨噬细胞炎症反应的精细调节机制。我们的研究结果阐明了 miR-146a 在与烟曲霉感染相关的人类疾病发病机制中的关键作用。
