Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solnavägen 9, SE-17165, Solna, Sweden.
Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Tomtebodavägen 18, SE-17177, Solna, Sweden.
Sci Rep. 2023 Oct 27;13(1):18423. doi: 10.1038/s41598-023-45590-6.
The lethal malaria parasite Plasmodium falciparum needs to constantly respond and adapt to changes within the human host in order to survive and transmit. One such change is composed of nutritional limitation, which is augmented with increased parasite loads and intimately linked to severe disease development. Extracellular vesicles released from infected red blood cells have been proposed as important mediators of disease pathogenesis and intercellular communication but whether important for the parasite response to nutritional availability is unknown. Therefore, we investigated the abundance and small RNA cargo of extracellular vesicles released upon short-term nutritional starvation of P. falciparum in vitro cultures. We show that primarily ring-stage parasite cultures respond to glucose and amino acid deprivation with an increased release of extracellular vesicles. Small RNA sequencing of these extracellular vesicles further revealed human miRNAs and parasitic tRNA fragments as the main constituent biotypes. Short-term starvations led to alterations in the transcriptomic profile, most notably in terms of the over-represented biotypes. These data suggest a potential role for extracellular vesicles released from P. falciparum infected red blood cells in the response to nutritional perturbations, their potential as prognostic biomarkers and point towards an evolutionary conserved role among protozoan parasites.
致命的疟原虫恶性疟原虫需要不断地对人体宿主内的变化做出反应和适应，以存活和传播。其中一种变化是营养限制，它伴随着寄生虫负荷的增加而加剧，并与严重疾病的发展密切相关。从感染的红细胞中释放的细胞外囊泡被认为是疾病发病机制和细胞间通讯的重要介质，但对于寄生虫对营养供应的反应是否重要尚不清楚。因此，我们研究了体外培养的恶性疟原虫在短期营养饥饿时释放的细胞外囊泡的丰度和小 RNA 货物。我们发现，主要处于环早期的寄生虫培养物对葡萄糖和氨基酸缺乏的反应是细胞外囊泡的释放增加。对这些细胞外囊泡的小 RNA 测序进一步显示，人类 miRNA 和寄生 tRNA 片段是主要的构成生物型。短期饥饿导致转录组谱发生改变，最明显的是代表性生物型的增加。这些数据表明，从感染的红细胞中释放的细胞外囊泡在对营养扰动的反应中可能具有潜在的作用，它们可能作为预后生物标志物，并指出在原生动物寄生虫中存在保守的作用。
