United States Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland, USA.
Infect Immun. 2013 Jul;81(7):2546-53. doi: 10.1128/IAI.01047-12. Epub 2013 May 6.
Heligmosomoides bakeri is a nematode with parasitic development exclusively in the small intestine of infected mice that induces a potent STAT6-dependent Th2 immune response. We previously demonstrated that host protective expulsion of adult H. bakeri worms from a challenge infection was delayed in selenium (Se)-deficient mice. In order to explore mechanisms associated with the delayed expulsion, 3-week-old female BALB/c mice were placed on a torula yeast-based diet with or without 0.2 ppm Se, and after 5 weeks, they were inoculated with H. bakeri infective third-stage larvae (L3s). Two weeks after inoculation, the mice were treated with an anthelmintic and then rested, reinoculated with L3s, and evaluated at various times after reinoculation. Analysis of gene expression in parasite-induced cysts and surrounding tissue isolated from the intestine of infected mice showed that the local-tissue Th2 response was decreased in Se-deficient mice compared to that in Se-adequate mice. In addition, adult worms recovered from Se-deficient mice had higher ATP levels than worms from Se-adequate mice, indicating greater metabolic activity in the face of a suboptimal Se-dependent local immune response. Notably, the process of worm expulsion was restored within 2 to 4 days after feeding a Se-adequate diet to Se-deficient mice. Expulsion was associated with an increased local expression of Th2-associated genes in the small intestine, intestinal glutathione peroxidase activity, secreted Relm-β protein, anti-H. bakeri IgG1 production, and reduced worm fecundity and ATP-dependent metabolic activity.
贝氏副柔线虫是一种专性寄生在感染小鼠小肠内的线虫,可诱导强烈的依赖 STAT6 的 Th2 免疫应答。我们之前的研究表明,硒(Se)缺乏的小鼠对感染性挑战的成虫 Heligmosomoides bakeri 的保护性驱逐被延迟。为了探索与延迟驱逐相关的机制,将 3 周龄雌性 BALB/c 小鼠置于含或不含 0.2 ppm Se 的酿酒酵母基础饮食中,5 周后,用 H. bakeri 感染性第三期幼虫(L3)接种。接种后 2 周,用驱虫剂处理小鼠,然后休息,再次接种 L3,并在再次接种后不同时间进行评估。分析寄生虫诱导的包囊和从感染小鼠肠道分离的周围组织中的基因表达显示,与 Se 充足小鼠相比,Se 缺乏小鼠的局部组织 Th2 反应降低。此外,从 Se 缺乏小鼠中回收的成虫的 ATP 水平高于 Se 充足小鼠中的成虫,表明在 Se 依赖的局部免疫应答不足的情况下具有更高的代谢活性。值得注意的是,在给 Se 缺乏的小鼠喂食 Se 充足的饮食后,驱逐过程在 2 至 4 天内恢复。驱逐与小肠中 Th2 相关基因的局部表达增加、肠谷胱甘肽过氧化物酶活性、分泌的 Relm-β 蛋白、抗 H. bakeri IgG1 产生以及减少的蠕虫生殖力和 ATP 依赖性代谢活性相关。