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Interleukin 17A Derived from γδ T Cell Induces Demyelination of the Brain in Angiostrongylus cantonensis Infection

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Abstract

Angiostrongylus cantonensis infection is a typical cause of eosinophilic encephalitis (EM), which has been reported to induce serious damage in the central nervous system. Both parasite and host factors contribute to the onset of EM, but the related immune-inflammation pathogenesis remains poorly characterised. An A. cantonensis infection model was generated through the infection of mice by gavage. Transmission electron microscopy and immunohistochemistry were used to assess the pathologic changes in the brain. The mRNA expression of inflammatory factors was tested using qRT-PCR. A combination of flow cytometry and western blotting was used to evaluate the alteration of leukocytes and related cytokines. A critical role of IL-17 was found by injecting IL-17A monoclonal antibody into naïve and A. cantonensis-infected mice. A. cantonensis larvae altered the immune homeostasis in the brain, leading to the destruction of myelin sheaths and activation of microglia and macrophage. During this process, IL-17A accumulation was observed, and IL-17RA was expressed in oligodendrocytes and microglia during the infection. Notably, γδ T cell was the major origin of IL-17A production induced by the parasite. After an IL-17A-neutralising antibody was applied, alterations in myelination and the state of the microglia/macrophage were discovered; the neurobehavioural scores of the mice also improved. Our study reveals one unrecognised impact of the γδ T cells in parasitic encephalopathy and emphasises that blocking IL-17A signalling can attenuate microglia and macrophage activation, thus reducing CNS demyelination and ameliorating the neurobehavioural deficit in A. cantonensis-infected mice.

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Funding

This work was supported by the National Natural Science Foundation of China (no. 81401688); Fundamental Research Funds for the Central Universities, SCUT (No. 2018MS81); Medical Scientific Research Foundation of Guangdong Province (No. A2018362); Fundamental Research Funds for the Central Universities (no. 2017MS090); South China University of Technology Scientific Research Funding (no. D6172910); and Medical Scientific Research Foundation of Guangdong Province (No. A2018362).

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  1. Ying Feng and Zongpu Zhou contributed equally to this work.

Authors and Affiliations

  1. School of Medicine, South China University of Technology, Guangzhou, 510006, China

    Ying Feng, Zongpu Zhou & Zhen Liu

  2. Department of Blood Transfusion, Guangzhou First People’s Hospital, Guangzhou, 510180, Guangdong, China

    Zhen Liu

  3. Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China

    Cunjing Zheng, Fukang Xie & Zhong-Dao Wu

  4. The Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510080, China

    Feng Feng

  5. Key Laboratory of Tropical Disease Control, Ministry of Education, Guangzhou, 510080, China

    Zhong-Dao Wu

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Contributions

Zongpu Zhou, Zhen Liu, Cunjing Zheng, and Feng Feng carried out the experiments and performed the statistical analyses. Zongpu Zhou drafted the manuscript. Zhong-Dao Wu, Fukang Xie, and Ying Feng conceived and coordinated the study. All authors read and approved the final manuscript.

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Correspondence to Ying Feng or Zhong-Dao Wu.

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All procedures applied to the canines were approved by the Institutional Animal Care and Use Committee of Sun Yat-Sen University and approved by the Laboratory Animal Regulations of Guangdong Province. Animal welfare was in compliance with Laboratory animal Guideline for Ethical Review of Animal Welfare, General Administration of Quality Supervision, Inspection and Quarantine of the People’s Republic of China/Standardization Administration of China (GB/T35892-2018).

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Feng, Y., Zhou, Z., Liu, Z. et al. Interleukin 17A Derived from γδ T Cell Induces Demyelination of the Brain in Angiostrongylus cantonensis Infection. Mol Neurobiol 58, 3968–3982 (2021). https://doi.org/10.1007/s12035-021-02366-1

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