Interleukin 17-producing γδ T cell induced demyelination of brain during Angiostrongylus cantonensis infection

Abstract Background: Angiostrongylus cantonensis infection is one typical reason 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 remain poorly characterized.Methods: A. cantonensis infection model was generated through infecting mice by gavage. TEM and IF were used to assess the pathologic changes of brain. The mRNA expression of inflammatory factors was tested by qRT-PCR. Combining flow cytometry with western blotting to evaluate the alteration of inflammatory cells and related cytokines. Critical role of IL-17 was found, to evaluate the function of IL-17A, we injected IL-17A mAb to naive and A. cantonensis infected mice. Results: A. cantonensis larvae altered immune homeostasis in the brain, led to the destruction of myelin shealth and activation of microglia. IL-17A accumulation was observed, IL-17RA was expressed on oligodendrocyte and microglia during the infection. More important, γδ T cells are the source of IL-17A induced by parasite. After IL-17A neutralizing antibody was applied, alterations of microglia state and myelination were discorved, mice neurobehavioral test also improved.Conclusion: Our study reveals a previously unrecognized impact of the IL-17+ γδ T cells in parasitic encephalopathy and emphasizes that blocking IL17A signaling can attenuate microglia activation, thus reducing CNS demyelination and ameliorate behavioral deficit in A. cantonensis infected mice.