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Tim-3/Galectin-9 signaling pathway is involved in the cytokine changes in mice with alveolar echinococcosis

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Abstract

Background

Tim-3/Galectin-9 is involved in the immune escape of many pathogens. However, the role of Tim-3/Galectin-9 in persistent infection of Echinococcus multilocularis (Em), which is related to immune escape, is still unclear.

Objective

To investigate the role of Tim-3/Galectin-9 and related cytokines in mice with persistent infection of Em.

Methods

Em infection model was established by injecting the protoscoleces. Serum was collected at days 2, 8, 30, 60, 90, 180 and 270 after infection. Lymphocytes were isolated from liver tissue samples with Ficoll. Tim-3 + CD4 + T percentage was analyzed by flow cytometry. CD4 + T cells were isolated from liver tissues of Em infected mice and cultured in vitro. The mRNA levels of Tim-3, Galectin-9, IFN-γ and IL-4 were detected by qRT-PCR. Cytokine levels in serum and culture supernatant (IFN-γ and IL-4) were analyzed by cytometric bead array.

Results

The expression of Tim-3 and Galectin-9 mRNA significantly increased after 30 days of infection, reached peak on day 90, and then decreased slightly on days 180–270. The expression of IFN-γ mRNA, increased on day 2 and 8 after infection, slightly decreased on days 30–60, and obvious decreased on days 90–270, but were still higher than those of the control group. The expression of IL-4 mRNA gradually increased along with the time of infection. In serum of Em infected mice, level of IFN-γ peaked at day 30 and then gradually decreased; whereas IL-4 level peaked at day 90 and then gradually decreased. In vitro experiment found that Tim-3/Galectin-9 directly caused the changes in the levels of IFN-γ and IL-4.

Conclusions

Tim-3/Galectin-9 signaling pathway may be involved in the development of persistent infection of Em by regulating the production of Th1 and Th2 cytokines.

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Availability of data and material

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

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Funding

This work was supported by the National Natural Science Foundation of China [grant numbers 81960373, 81460307, 81660343, 81160200, 81160202, 81060135] and Xinjiang Institute of Hydatid Disease [grant number XJDX0202-2010-04].

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Authors and Affiliations

  1. Department of Clinical Laboratory, Tumor Hospital Affiliated to Xinjiang Medical University, 830011, Urumqi, China

    Shaoyu Li & Nannan Pang

  2. Reproductive Medicine Center, First Affiliated Hospital of Xinjiang Medical University, 830011, Urumqi, Xinjiang, China

    Yuejie Zhu

  3. Department of Immunology, College of Basic Medicine, Xinjiang Medical University, No. 393, Xinyi Road, 830011, Urumqi, Xinjiang, China

    Song Wang & Jianbing Ding

  4. Department of Clinical Laboratory, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, Urumqi, China

    Yujiao Li, Mengting An & Fengbo Zhang

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  1. Shaoyu Li
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  2. Yuejie Zhu
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  3. Song Wang
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Contributions

JBD and HNF conceived and designed the experiments. SYL, FBZ, YJZ and YJL performed the experiments. HNF, NNP and MTA analyzed the data. SYL, FBZ, HNF Fan and JBD wrote the manuscript.

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Correspondence to Fengbo Zhang or Jianbing Ding.

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The authors declare that there is no conflict of interest.

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All animal experiments were conducted according to the ethical guidelines of the Animal Care and Use Committee and were approved by the Ethical Committee of First Affiliated Hospital of Xinjiang Medical University (License number: A-20130216-155).

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Shaoyu Li, Yuejie Zhu and Song Wang authors contributed equally to this work.

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Li, S., Zhu, Y., Wang, S. et al. Tim-3/Galectin-9 signaling pathway is involved in the cytokine changes in mice with alveolar echinococcosis. Mol Biol Rep 49, 7497–7506 (2022). https://doi.org/10.1007/s11033-022-07554-3

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  • DOI: https://doi.org/10.1007/s11033-022-07554-3

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