The Role And Pathogenicity Mechanism Of IL-17A In Demyelination Induced By Angiostrongylus Cantonensis Infection

Demyelinating disease of the central nervous system is one of the most common neurological diseases.Our results showed that infection with Angiostrongylus cantonensis induced demyelination of the brain,during which IL-17A expression was significantly increased.Therefore,we speculated that IL-17A might play an important role in the demyelination injury caused by A.cantonensis infection.To test this hypothesis,we established a model of central nervous system injury in BALB/c mice by intragastric administration of A.cantonensis larvae,and identified the demyelinating injury in the corpus callosum of mice by transmission electron microscopy.At the same time,the expression of IL-17A and IL-17RA the source of IL-17A in the brain were detected by qRT-PCR and flow cytometry.Next,we injected neutralizing antibodies against IL-17A to decrease IL-17A level during A.cantonensis infection,and then observed whether the myelin sheath injury in infected mice was altered.Finally,immunofluorescence,qPCR,Western Blotting and other techniques were used to detect the activation status of microglia and astrocytes in the brain of A.cantonensis infected mice before and after the injection of neutralizing antibody against IL-17A,and IL-17A was applied to oligoendrocytes and astrocytes in vitro.The results showed that A.cantonensis infection led to demyelination of the corpus callosum region,accompanied by activation of A1/A2 type astrocytes and M1/M2 type microglia in the brain.The expression levels of IL-17A and IL-17RA were increased,and the γδ T cells stored in the brain were the main source of IL-17A.Inhibiting IL-17A significantly alleviated demyelination damage in A.cantonensis infected mice,and the activation degree of A1 type astrocytes and M1/M2 type microglia was also reduced.In vitro experiments showed that IL-17A could not only directly damage oligoendrocytes,but also indirectly damage oligoendrocytes by activating A1 astrocytes and increasing SOCS3 expression in these cells.Therefore,we concluded that IL-17A plays an important role in demyelination induced by A.cantonensis infection,and the mechanism may be realized by increasing the expression of SOCS3 in A1 type astrocytes.Specific blocking of IL-17A can be considered as a potential target for the treatment of neuroinflammatory demyelinating diseases associated with astrocyte activation.