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SiO2 prompts host defense against Acinetobacter baumannii infection by mTORC1 activation

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Abstract

Host-pathogen interactions in the setting of chronic pulmonary inflammation remain unclear, and the occurrence of pneumonia is increased in patients with chronic obstructive pulmonary disease who use immunosuppressive drugs. We performed Acinetobacter baumannii infection in mice with chronic pulmonary inflammation after intranasal administration of SiO2 and found SiO2 treatment increased host defense against A. baumannii infection. Innate immune responses initiated by NF-κB, type 1 interferon, NLRP3 and AIM2 inflammasomes were dispensable for SiO2-mediated host defense. SiO2 treatment activated the mTORC1 signaling, and mTORC1 was crucial for host defense against A. baumannii infection. Our study highlights the protective role of mTORC1 signaling in host defense against bacterial infection, offers novel insights into understanding the mechanisms of immunosuppressive drug-related pneumonia, and provides potential host-directed therapeutics to treat bacterial infections.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2017YFD0500300), the National Natural Science Foundation of China (31970896, 31701134 and 81701578) and Yunnan Province (2019FJ008, 2018FA038, 2018FB127, 2018FB131, HXDTZX-2019-1, HXDT-2019-2, and AMHD-2018-2). We thank F. Shao (National Institute of Biological Sciences, Beijing) for Ifnar−/− and Aim2−/− mice; and D. Wang (Zhejiang University) for Nlrp3−/− mice.

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Authors and Affiliations

  1. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China

    Xiaomin Guo, Chaoming Wang, Tao Xu & Xiaopeng Qi

  2. Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China

    Xiaomin Guo & Xiaopeng Qi

  3. Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China

    Lu Yang & Chaohong Liu

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  1. Xiaomin Guo
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  2. Chaoming Wang
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  3. Tao Xu
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  4. Lu Yang
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  5. Chaohong Liu
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  6. Xiaopeng Qi
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Correspondence to Xiaopeng Qi.

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Guo, X., Wang, C., Xu, T. et al. SiO2 prompts host defense against Acinetobacter baumannii infection by mTORC1 activation. Sci. China Life Sci. 64, 982–990 (2021). https://doi.org/10.1007/s11427-020-1781-8

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  • DOI: https://doi.org/10.1007/s11427-020-1781-8

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