Modulatory Effects of Hydatid Cyst Fluid on a Mouse Model of Experimental Autoimmune Encephalomyelitis

VETERINARY SCIENCES(2024)

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Simple Summary Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and demyelination of the central nervous system. The hygiene hypothesis suggests that a decrease in exposure to parasites may contribute to an increase in MS incidence. We hypothesized that cystic echinococcosis (CE), which is caused by the helminth Echinococcus granulosus, could potentially reduce the severity of MS. To investigate this, we used mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. The mice were injected with hydatid cyst fluid (HCF) from E. granulosus cysts. The HCF shifted the immune response from a pro-inflammatory Th1 to an anti-inflammatory Th2, resulting in a decrease in IFN-gamma and an increase in IL-4. As a result, the HCF delayed the onset of EAE and reduced its severity. This led to the prevention of weight loss and a decrease in inflammation and demyelination in the spinal cord.Abstract The reduced burden of helminth parasites in industrialized countries is probably one of the reasons for the increased prevalence of autoimmune disorders such as multiple sclerosis (MS). The current study aimed to evaluate the potential preventive effects of hydatid cyst fluid (HCF) on the disease severity in an EAE mouse model of MS. EAE-induced mice were treated with HCF before and after EAE induction. An RT-PCR-based evaluation of IFN-gamma, IL-1 beta, TNF, T-bet, IL-4, GATA3, IL-17, RoR gamma, TGF-beta, and FOXP3 expression levels in splenocytes and an ELISA-based analysis of IFN-gamma and IL-4 levels in cell culture supernatant of splenocytes were performed. Histopathological examinations of mice during the study were also conducted. The expression levels of T-bet, IL-4, GATA3, TGF-beta, and FOXP3 in EAE + HCF mice were significantly higher compared to EAE + PBS mice. In the EAE + HCF group, the expression levels of IFN-gamma, IL-1 beta, and TNF were significantly lower than in the EAE + PBS group. The histopathological results showed significantly reduced inflammation and demyelination in EAE + HCF mice compared to EAE + PBS mice. Our study provides proof-of-concept in the EAE mouse model of MS that helminth-derived products such as HCF have a potential prophylactic effect on MS development and present a novel potential therapeutic strategy.
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关键词
experimental autoimmune encephalomyelitis,multiple sclerosis,helminth immunotherapy,cystic echinococcosis,hydatid cyst
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