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Interleukin 17A Derived from γδ T Cell Induces Demyelination of the Brain in Angiostrongylus cantonensis Infection.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2021 Aug; Vol. 58 (8), pp. 3968-3982. Date of Electronic Publication: 2021 Apr 26. - Publication Year :
- 2021
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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.<br /> (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Brain immunology
Demyelinating Diseases immunology
Intraepithelial Lymphocytes immunology
Male
Mice
Mice, Inbred BALB C
Microglia immunology
Microglia metabolism
Strongylida Infections immunology
Brain metabolism
Demyelinating Diseases metabolism
Interleukin-17 biosynthesis
Intraepithelial Lymphocytes metabolism
Strongylida Infections metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 58
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 33904019
- Full Text :
- https://doi.org/10.1007/s12035-021-02366-1