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MiR-146a Negatively Regulates Aspergillus fumigatus-Induced TNF-α and IL-6 Secretion in THP-1 Macrophages

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Abstract

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.

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Acknowledgements

This work was supported by grants from National Natural Science Foundation of China (No. 81773338, 81773342, 81502739), CAMS Innovation Fund for Medical Sciences (2017-I2M-1-017, 2016-I2M-1-005), “Thirteen Five” Key Medical Talent’s Project in Science and Education of Jiangsu Province (ZDRCB2016010), Jiangsu R&D program social development project (No. BE2015717), Jiang Su National Natural Science Foundation (No. BK20150068, No. BK20190144), PUMC Youth Fund (No. 3332016108).

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  1. Jianbo Tong, Zhimin Duan, and Rong Zeng have contributed equally to this article.

Authors and Affiliations

  1. 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

    Jianbo Tong, Zhimin Duan, Rong Zeng, Leilei Du, Song Xu, Liwei Wang, Yuzhen Liu, Xu Chen & Min Li

  2. Department of Dermatology, First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, 330001, People’s Republic of China

    Jianbo Tong

  3. Jiangsu Province Blood Center, Nanjing, 210042, Jiangsu, People’s Republic of China

    Qing Chen

  4. Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 100005, Beijing, People’s Republic of China

    Qing Chen & Min Li

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Jianbo Tong and Xu Chen wrote the main manuscript text. Jianbo Tong, Zhimin Duan, Rong Zeng, Leilei Du, Song Xu, Liwei Wang and Yuzhen Liu jointly performed the experiments, prepared all figures and performed statistical analysis in this work. Qing Chen, Xu Chen and Min Li supervised the experimental design and revised manuscript text. Qing Chen, Xu Chen and Min Li are the corresponding authors. All authors reviewed the manuscript.

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Correspondence to Qing Chen, Xu Chen or Min Li.

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Tong, J., Duan, Z., Zeng, R. et al. MiR-146a Negatively Regulates Aspergillus fumigatus-Induced TNF-α and IL-6 Secretion in THP-1 Macrophages. Mycopathologia 186, 341–354 (2021). https://doi.org/10.1007/s11046-021-00538-0

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