摘要
[目的]弓形虫(Toxoplasma gondii)是一种可以寄生于几乎所有温血动物有核细胞内的原生动物寄生虫,其感染可导致宿主脾脏和外周血T细胞耗竭关键分子T细胞免疫球蛋白粘蛋白-3(T cell immunoglobulin and mucin domain-containing protein 3,TIM-3)表达上调,进而抑制免疫应答。已有研究证实α-乳糖能特异性调节TIM-3与其配体半乳糖凝集素9(Galectin-9,Gal-9)的相互作用,进而减弱其抑制功能,增强机体抗感染能力。评估α-乳糖通过竞争性结合TIM-3配体Gal-9对感染弓形虫不同毒力株(RH株和ME49株)小鼠的免疫病理的干预效果,以期为弓形虫感染的免疫调节治疗提供新策略。[方法]利用弓形虫感染小鼠模型,皮下注射α-乳糖后,分析小鼠生存率、脾指数及肺脏、脾脏组织病理学变化,并通过流式细胞术检测小鼠外周血淋巴细胞亚群的比例及其表面免疫检查点分子含免疫球蛋白(Immunoglobulin,Ig)及ITIM结构域的T细胞免疫受体(T cell immunoreceptor with Ig and ITIM domains,TIGIT)的表达情况。[结果]α-乳糖处理虽延长弓形虫感染小鼠的存活时间,但对脾指数及肺、脾组织的病理损伤无改善作用。此外,感染弓形虫后,小鼠外周血中不同淋巴细胞亚群(包括CD8⁺T细胞、NK细胞等)的TIGIT表达均未因α-乳糖处理而出现显著升高。[结论]α-乳糖对感染弓形虫的小鼠无显著影响,这可能与虫株毒力及宿主免疫衰竭状态相关。
[Objective]Toxoplasma gondii,a protozoan parasite that can parasitize in the nucleated cells of almost all warm-blooded animals.Its infection can upregulate the expression of key exhaustion molecule,T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)of host's spleen and peripheral blood T cells,thereby inhibiting the immune response.Previous studies showed thatα-lactose can specifically regulate the interaction between TIM-3 and its ligand Galectin-9(Gal-9),thereby weakening its inhibitory function and enhancing host's anti-infection ability.This study aims to evaluate the immunopathological modulatory effects ofα-lactose,mediated by its competitive binding to the TIM-3 ligand Gal-9,in mice infected with different virulent strains of Toxoplasma gondii(RH and ME49).To provide a new strategy for the immunomodulatory treatment of Toxoplasma gondii infection.[Methods]Using a Toxoplasma gondii-infected mouse model,mouse survival rates,spleen indices,and histopathological changes in the lungs and spleen were analyzed afterα-lactose was administered via subcutaneous injection.Additionally,flow cytometry was used to assess the proportions of peripheral blood lymphocyte subsets and the expression of T cell immunoreceptor with Ig and ITIM domains(TIGIT)-an immune checkpoint molecule-on the cell surface.[Results]Althoughα-lactose treatment prolonged the survival time of mice infected with Toxoplasma gondii,it did not improve the spleen index or the histopathological damage in the lungs and spleens.Furthermore,α-lactose treatment did not significantly increase TIGIT expression on different peripheral blood lymphocyte subsets(including CD8⁺T cells and NK cells)in mice following Toxoplasma gondii infection.[Conclusion]α-lactose did not significantly influence the mice infection with Toxoplasma gondii,which may be related to the virulence of the parasite strain and the state of host immune exhaustion.
作者
张义伟
李洪宇
景钰淇
孙露
姜宁
ZHANG Yiwei;LI Hongyu;JING Yuqi;SUN Lu;JIANG Ning(College of Animal Science and Veterinary Medicine/Key Laboratory of Livestock Infectious Diseases,Ministry of Education,Shenyang Agricultural University,Shenyang 110161,China)
出处
《沈阳农业大学学报》
北大核心
2025年第5期44-51,共8页
Journal of Shenyang Agricultural University
基金
国家重点研发计划项目(2023YFD1802403)
沈阳农业大学公开招聘博士毕业生科研启动费项目(880421011)。
