黉聚讲座系列——Gaucher disease protects against tuberculosis

日期: 2023-09-03 访问数:

【讲座题目】Gaucher disease protects against tuberculosis

【主讲人】范婧雯 博士(法国巴斯德研究所)


【地点】生命科学学院 E307学术报告厅

【邀请人】韩家淮 教授

【主讲人介绍】范婧雯,法国巴斯德研究所博士后。2017年毕业于厦门大学生命科学学院,获学士学位。2022年毕业于剑桥大学,获博士学位。厦门大学博伊特勒书院首届拔尖班毕业生。先后获剑桥大学Gates Scholarship,巴斯德基金会Gillings Fellowship。

【报告摘要】Biallelic mutations in the glucocerebrosidase (GBA1) gene cause Gaucher disease, characterized by lysosomal accumulation of glucosylceramide and glucosylsphingosine in macrophages. Gaucher and other lysosomal diseases occur with high frequency in Ashkenazi Jews. It has been proposed that the underlying mutations confer a selective advantage, in particular conferring protection against tuberculosis. Here, using a zebrafish Gaucher disease model, we find that the mutation GBA1 N370S, predominant among Ashkenazi Jews, increases resistance to tuberculosis through the microbicidal activity of glucosylsphingosine in macrophage lysosomes. Consistent with lysosomal accumulation occurring only in homozygotes, heterozygotes remain susceptible to tuberculosis. Thus, our findings reveal a mechanistic basis for protection against tuberculosis by GBA1 N370S and provide biological plausibility for its selection if the relatively mild deleterious effects in homozygotes were offset by significant protection against tuberculosis, a rampant killer of the young in Europe through the Middle Ages into the 19th century.

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