来自非免疫蛋白质的酸通过抗微生物和免疫调节特性向感染
Marcelo D T Torres1, Angela Cesaro1, Cesar de la Fuente-Nunez1
1Machine Biology Group, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA; Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA; Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA, USA.
来自非免疫人类蛋白质的新型抗微生物对细菌病原体表现出强烈的活性. 这些分子还调节免疫反应,并在临床前模型中证明了抗感染功效,扩大了已知的宿主免疫范围.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 加密 (EP) 是一种新型的抗微生物分子类别,在宿主免疫力中具有潜在的作用.
- 许多EP存在于与免疫系统无关的蛋白质中,这表明了更广泛的免疫功能.
- 传统的抗生素面临着越来越多的抗菌素耐药性的挑战.
研究的目的:
- 研究来自非免疫人类蛋白质的的抗微生物和免疫调节性质.
- 为了确定这些是否可以作为常规抗生素的替代品.
- 探索宿主免疫系统已知的组件的潜在扩张.
主要方法:
- 来自非免疫人类蛋白质的代表性的合成和体外分析.
- 对抗细菌病原体的抗微生物活性的评估,包括作用机制 (膜向).
- 在小鼠模型中评估免疫调节作用对炎症媒介 (IL-6,TNF-α,MCP-1) 和体内抗感染功效.
主要成果:
- 来自非免疫蛋白质的,包括结构性,神经和视觉系统蛋白质,表现出强大的体外抗菌活性.
- 观察到同一个身体区域的的协同抗微生物效应.
- 近90%的测试显示出免疫调节作用,8个在小鼠模型中显示出显著的抗感染功效,减少了高达1万倍的细菌负载.
结论:
- 来自非免疫人类蛋白质的具有显著的抗微生物和免疫调节功能.
- 这些发现支持了非免疫蛋白质有助于宿主免疫的假设.
- 这项研究扩大了对免疫系统的理解,包括以前未知的保护性.
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