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Acinetobacter baumannii reinforces the pathogenesis by promoting IL-17 production in a mouse pneumonia model

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Abstract

Interleukin-17 (IL-17) is involved in host defense against bacterial infection. Little is known about the role of IL-17 in A. baumannii-infected pneumonia. Our objective was to investigate the role of IL-17 in pulmonary A. baumannii infection in a mouse model. We infected C57BL/6 mice intra-tracheally (i.t.) with A. baumannii to establish pneumonia model and found A. baumannii infection elevated IL-17 expression in lungs. IL-17-deficient (Il17−/−) mice were resistant to pulmonary A. baumannii infection, showing improved mice survival, reduced bacteria burdens, and alleviated lung inflammation. Further, treatment of A. baumannii-infected Il17−/− mice with IL-17 exacerbated the severity of pneumonia. These data suggest a pathogenic role of IL-17 in pulmonary A. baumannii infection. Further, the infiltration and phagocytic function of neutrophils in broncho-alveolar lavage fluid were detected by flow cytometry. The results showed that Il17−/− mice had increased neutrophil infiltration and enhanced phagocytosis in neutrophils at the early time of infection. Treatment of mice with IL-17 suppressed phagocytic function of neutrophils. All data suggest that IL-17 promotes susceptibility of mice to pulmonary A. baumannii infection by suppressing neutrophil phagocytosis at early time of infection. Targeting IL-17 might be a potential therapeutic strategy in controlling the outcome of A. baumannii pneumonia.

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Data availability

RNAseq data of innate immune response of lung to A. baumannii infection were deposited in GEO database with the accession number GSE143597.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (NSFC) [grant number 81971561] and 1 3 5 project for disciplines of excellence, West China Hospital, Sichuan University [grant number ZYXY21004].

Funding

National Natural Science Foundation of China, 81971561, Yun Shi, West China Hospital, Sichuan University, 135 project for disciplines of excellence (No. ZYXY21004), Yun Shi.

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Author notes

  1. Yangyang Zhou and Chuanying Xiang contributed equally to this work.

Authors and Affiliations

  1. West China Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

    Yangyang Zhou, Chuanying Xiang, Ning Wang, Xiaomin Zhang, Yu Xie, Hong Yang, Gang Guo, Kaiyun Liu, Yan Li & Yun Shi

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  1. Yangyang Zhou
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Contributions

All authors contributed to the study conception and design. Most of experiments and analysis were performed by Yangyang Zhou and Chuanying Xiang. Ning Wang, Xiaomin Zhang, Yu Xie, Hong Yang contributed to material preparation, technical support and data analysis. Gang Guo, and Kaiyun Liu contributed to the data analysis, resource and technical help. The first draft of the manuscript was written by Yangyang Zhou and Chuanying Xiang. Yun Shi and Yan Li conceived ideas and edited the manuscript. All authors commented on previous versions of the manuscript and approved the final manuscript.

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Correspondence to Yan Li or Yun Shi.

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Zhou, Y., Xiang, C., Wang, N. et al. Acinetobacter baumannii reinforces the pathogenesis by promoting IL-17 production in a mouse pneumonia model. Med Microbiol Immunol 212, 65–73 (2023). https://doi.org/10.1007/s00430-022-00757-2

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