肠道微生物群引发了针对疟疾传播的保护性免疫反应
Bahtiyar Yilmaz1, Silvia Portugal2, Tuan M Tran2
1Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
Cell
|December 7, 2014
概括
不激活UDP-银糖:β-银酸-α1-3-银酸转移酶 (α1,3GT) 基因可以预防疟疾. 通过这种基因失活产生的抗α-gal抗体向Plasmodium寄生虫,提供对感染的保护.
科学领域:
- 免疫学 免疫学 免疫学
- 进化生物学 进化生物学
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 糖基化对于抗感染能力至关重要,并受自然选择的影响.
- 这种Galα1-3Galβ1-4GlcNAc-R (α-gal) 甘氨酸是由像Plasmodium spp.这样的病原体表达的. 和一些细菌.
- 人类通常缺乏α-gal,原因是UDP-Galactose:β-galactoside-α1-3-galactosyltransferase (α1,3GT) 基因的失活,导致抗α-gal抗体的产生.
研究的目的:
- 调查α-gal表达的缺失是否能保护人免受Plasmodium感染.
- 确定抗α-gal抗体在疟疾传播和宿主防御中的作用.
主要方法:
- 研究了α1,3GT基因失活及其对α-gal表达的影响.
- 在Plasmodium spp.上分析了α-gal的存在. 和大肠杆菌 E. coli O86:B7.
- 评估了抗α-gal抗体与人类和α1,3GT缺乏小鼠的疟疾保护的相关性.
- 研究了抗α-gal抗体介导的寄生虫清除机制.
- 在小鼠模型中评估了针对α-gal进行疟疾保护的疫苗接种.
主要成果:
- 这两种都是Plasmodium spp. 和大肠杆菌O86:B7表达α-糖.
- 抗α-gal抗体与保护人类免受疟疾传播有关.
- 被大肠杆菌O86:B7殖民的α1,3GT缺乏的小鼠产生了保护性抗α-gal抗体.
- 抗α-gal抗体诱导补充介导的细胞毒性对皮肤中的Plasmodium杂虫.
- 针对α-gal的疫苗在小鼠中提供了对疟疾的无菌保护.
结论:
- 缺少α-gal表达和存在抗α-gal抗体,可以提供对疟疾的保护.
- 抗α-gal抗体在蚊子接种后立即中和Plasmodium寄生虫.
- 通过疫苗接种向α-gal糖是一种潜在的策略,可以减少人类的疟疾传播.
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