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弓形虫裂解物在自身免疫性脑脊髓炎C57BL/6小鼠模型中的免疫调节潜力

Immunomodulatory potential of Toxoplasma gondii lysate in C57BL/6 mouse model of autoimmune encephalomyelitis.

作者信息

Hajizadeh Maryam, Motavallihaghi Seyedmousa, Badakhsh Elham, Kazemi Tohid, Pagheh Abdol Sattar, Hatam-Nahavandi Kareem, Ahmadpour Ehsan

机构信息

Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

AMB Express. 2025 Jun 11;15(1):89. doi: 10.1186/s13568-025-01900-x.

DOI:10.1186/s13568-025-01900-x
PMID:40498142
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12158863/
Abstract

Multiple sclerosis (MS) is a debilitating autoimmune disease characterized by chronic inflammation and demyelination within the central nervous system. Immunotherapy is an essential part of managing MS symptoms and progression. This study aimed to evaluate the immunomodulatory effects of Toxoplasma gondii lysate antigens (TLA) in a C57BL/6 mouse model of experimental autoimmune encephalomyelitis (EAE). Eighteen mice were randomly assigned into three groups: healthy controls, EAE-induced mice, and EAE-induced mice treated with TLA. Clinical scores were recorded daily for all mice. To assess immune responses, mRNA and protein expression levels in isolated splenocytes were measured using quantitative real-time PCR and ELISA, respectively. In addition, histological analyses were performed to evaluate inflammation and demyelination across the experimental groups. TLA-treated mice exhibited significantly reduced clinical scores and demyelination compared to the untreated EAE group. The treatment also decreased inflammatory cell infiltration in CNS tissues. At the molecular level, TLA modulated cytokine expression by downregulating pro-inflammatory markers (IFN-γ, IL-17, RORγT) and upregulating anti-inflammatory and regulatory markers (IL-4, GATA3, FOXP3, TGF-β, TNF-α). TLA treatment demonstrated immunomodulatory and neuroprotective effects in EAE mice, suggesting its potential as a prophylactic or therapeutic agent in MS. These findings support further exploration of parasitic antigens in the context of autoimmune neuroinflammatory diseases.

摘要

多发性硬化症(MS)是一种使人衰弱的自身免疫性疾病,其特征是中枢神经系统内的慢性炎症和脱髓鞘。免疫疗法是控制MS症状和病情进展的重要组成部分。本研究旨在评估弓形虫裂解物抗原(TLA)在实验性自身免疫性脑脊髓炎(EAE)的C57BL/6小鼠模型中的免疫调节作用。18只小鼠被随机分为三组:健康对照组、诱导EAE的小鼠组和用TLA治疗的诱导EAE的小鼠组。每天记录所有小鼠的临床评分。为了评估免疫反应,分别使用定量实时PCR和ELISA测量分离的脾细胞中的mRNA和蛋白质表达水平。此外,进行组织学分析以评估各实验组的炎症和脱髓鞘情况。与未治疗的EAE组相比,接受TLA治疗的小鼠临床评分和脱髓鞘明显降低。该治疗还减少了中枢神经系统组织中的炎性细胞浸润。在分子水平上,TLA通过下调促炎标志物(IFN-γ、IL-17、RORγT)和上调抗炎及调节标志物(IL-4、GATA3、FOXP3、TGF-β、TNF-α)来调节细胞因子表达。TLA治疗在EAE小鼠中显示出免疫调节和神经保护作用,表明其作为MS预防或治疗剂的潜力。这些发现支持在自身免疫性神经炎症性疾病背景下进一步探索寄生虫抗原。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ad/12158863/41e3d686a0bf/13568_2025_1900_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ad/12158863/41e3d686a0bf/13568_2025_1900_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ad/12158863/3efd65586a1c/13568_2025_1900_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ad/12158863/c3988fd0619e/13568_2025_1900_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ad/12158863/44745052869b/13568_2025_1900_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ad/12158863/d0849c95486c/13568_2025_1900_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ad/12158863/41e3d686a0bf/13568_2025_1900_Fig5_HTML.jpg

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