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Sneaking Out for Happy Hour: Yeast-Based Approaches to Explore and Modulate Immune Response and Immune Evasion

机译:偷偷摸摸的欢乐时光:基于酵母的方法来探索和调节免疫反应和免疫逃避

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摘要

Many pathogens (virus, bacteria, fungi, or parasites) have developed a wide variety of mechanisms to evade their host immune system. The budding yeast Saccharomyces cerevisiae has successfully been used to decipher some of these immune evasion strategies. This includes the cis-acting mechanism that limits the expression of the oncogenic Epstein–Barr virus (EBV)-encoded EBNA1 and thus of antigenic peptides derived from this essential but highly antigenic viral protein. Studies based on budding yeast have also revealed the molecular bases of epigenetic switching or recombination underlying the silencing of all except one members of extended families of genes that encode closely related and highly antigenic surface proteins. This mechanism is exploited by several parasites (that include pathogens such as Plasmodium, Trypanosoma, Candida, or Pneumocystis) to alternate their surface antigens, thereby evading the immune system. Yeast can itself be a pathogen, and pathogenic fungi such as Candida albicans, which is phylogenetically very close to S. cerevisiae, have developed stealthiness strategies that include changes in their cell wall composition, or epitope-masking, to control production or exposure of highly antigenic but essential polysaccharides in their cell wall. Finally, due to the high antigenicity of its cell wall, yeast has been opportunistically exploited to create adjuvants and vectors for vaccination.
机译:许多病原体(病毒,细菌,真菌或寄生虫)已开发出多种逃避其宿主免疫系统的机制。出芽的酿酒酵母已成功用于破译某些免疫逃避策略。这包括顺式作用机制,该机制限制了致癌的爱泼斯坦-巴尔病毒(EBV)编码的EBNA1的表达,并因此限制了由这种必需但高度抗原性的病毒蛋白衍生的抗原肽的表达。基于发芽酵母的研究还揭示了沉默的表观遗传转换或重组的分子基础,除了编码紧密相关且高度抗原化的表面蛋白的扩展基因家族的一个成员外,所有其他基因均沉默。这种机制被几种寄生虫(包括病原体,如疟原虫,锥虫,念珠菌或肺孢子虫)利用来改变其表面抗原,从而逃避了免疫系统。酵母本身可以是病原体,病原真菌(如念珠菌)在系统发育上与酿酒酵母非常接近,因此已开发出隐身策略,包括改变其细胞壁组成或表位掩盖,以控制高产量的生产或暴露。细胞壁中的抗原性但必不可少的多糖。最后,由于其细胞壁的高度抗原性,酵母被机会性地开发以产生用于疫苗接种的佐剂和载体。

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