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A comparative study of IL-33 and its receptor ST2 in a C57BL/6 J mouse model of pulmonary Cryptococcus neoformans infection

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Abstract

It has been reported that IL-33 receptor ST2 deficiency mitigates Cryptococcus neoformans (C. neoformans) pulmonary infection in BALB/c mice. IL-33 may modulate immune responses in ST2-dependent and ST2-independent manners. The host genetic background (i.e., BALB/c, C57BL/6 J) influences immune responses against C. neoformans. In the present study, we aimed to explore the roles of IL-33 and ST2 in pulmonary C. neoformans-infected mice on a C57BL/6 J genetic background. C. neoformans infection increased IL-33 expression in lung tissues. IL-33 deficiency but not ST2 deficiency significantly extended the survival time of C. neoformans-infected mice. In contrast, either IL-33 or ST2 deficiency reduced fungal burdens in lung, spleen and brain tissues from the mice following C. neoformans intratracheal inoculation. Similarly, inflammatory responses in the lung tissues were more pronounced in both the IL-33−/− and ST2−/− infected mice. However, mucus production was decreased in IL-33−/− infected mice alone, and the level of IL-5 in bronchoalveolar lavage fluid (BALF) was substantially decreased in the IL-33−/− infected mice but not ST2−/− infected mice. Moreover, IL-33 deficiency but not ST2 deficiency increased iNOS-positive macrophages. At the early stage of infection, the reduced pulmonary fungal burden in the IL-33−/− and ST2−/− mice was accompanied by increased neutrophil infiltration. Collectively, IL-33 regulated pulmonary C. neoformans infection in an ST2-dependent and ST2-independent manner in C57BL/6 J mice.

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Data availability

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Acknowledgements

This research was supported by the Precision Medicine Research of the National Key Research and Development Plan of China (2016YFC0905800), the National Natural Science Foundation of China (82171738, 81671563, 81770031, and 81970031), and the Jiangsu Provincial Health and Family Planning Commission Foundation (Q2017001).

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Author notes

  1. Zhengxia Wang, Qiyun Ma and Jingxian Jiang contributed equally to the work.

Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Zhengxia Wang, Qiyun Ma, Jingxian Jiang, Mao Huang & Ningfei Ji

  2. Department of Respiratory and Critical Care Medicine, The Affiliated Huaian NO.1 People’s Hospital of Nanjing Medical University, Huaian, 223300, China

    Qiyun Ma

  3. The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, Jiangsu, China

    Xiaofan Yang

  4. NHC Key Laboratory of Antibody Technique, Jiangsu Province Engineering Research Center of Antibody Drug, Jiangsu Key Laboratory of Pathogen Biology, Department of Immunology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China

    Enrui Zhang, Yuan Tao & Mingshun Zhang

  5. Department of Pathology, Nanjing Chest Hospital, Nanjing, 210029, China

    Huidi Hu

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Contributions

ZW performed animal experiments and drafted the paper. QM analyzed the data. JJ performed the in vitro experiments. XY, EZ, YT and HH helped with improving the methodology. MH contributed to the paper revision. NJ and MZ designed and supervised the project.

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Correspondence to Mao Huang, Ningfei Ji or Mingshun Zhang.

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430_2022_755_MOESM1_ESM.tif

Supplementary file1 Figure S1 Flow cytometry for the gating strategy of cells in BALF. Flow cytometry shows the gating strategy of total cells (R2 gate) and neutrophils (R3 gate) of cryptococcal-infected mice in BALF. Refer to Figure 6B, 6C. (TIF 233 KB)

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Wang, Z., Ma, Q., Jiang, J. et al. A comparative study of IL-33 and its receptor ST2 in a C57BL/6 J mouse model of pulmonary Cryptococcus neoformans infection. Med Microbiol Immunol 212, 53–63 (2023). https://doi.org/10.1007/s00430-022-00755-4

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