Larrazabal Camilo, López-Osorio Sara, Velásquez Zahady D, Hermosilla Carlos, Taubert Anja, Silva Liliana M R
Institute of Parasitology, Biomedical Research Center Seltersberg, Justus Liebig University Giessen, 35392 Giessen, Germany.
CIBAV Research Group, Veterinary Medicine School, Faculty of Agrarian Sciences, University of Antioquia, Medellín 050010, Colombia.
Microorganisms. 2021 Nov 17;9(11):2372. doi: 10.3390/microorganisms9112372.
Coccidian parasites are obligate intracellular pathogens that affect humans and animals. Apicomplexans are defective in de novo synthesis of cholesterol, which is required for membrane biosynthesis and offspring formation. In consequence, cholesterol has to be scavenged from host cells. It is mainly taken up from extracellular sources via LDL particles; however, little is known on the role of HDL and its receptor SR-BI in this process. Here, we studied effects of the SR-BI-specific blocker BLT-1 on the development of different fast (, , ) and slow ( and replicating coccidian species. Overall, development of all these parasites was significantly inhibited by BLT-1 treatment indicating a common SR-BI-related key mechanism in the replication process. However, SR-BI gene transcription was not affected by and infections. Interestingly, BLT-1 treatment of infective stages reduced invasive capacities of all fast replicating parasites paralleled by a sustained increase in cytoplasmic Ca levels. Moreover, BLT1-mediated blockage of SR-BI led to enhanced host cell lipid droplet abundance and neutral lipid content, thereby confirming the importance of this receptor in general lipid metabolism. Finally, the current data suggest a conserved role of SR-BI for successful coccidian infections.
球虫寄生虫是专性细胞内病原体，可感染人类和动物。顶复门原虫在胆固醇的从头合成方面存在缺陷，而胆固醇是膜生物合成和子代形成所必需的。因此，胆固醇必须从宿主细胞中获取。它主要通过低密度脂蛋白颗粒从细胞外来源摄取；然而，关于高密度脂蛋白及其受体SR-BI在此过程中的作用知之甚少。在这里，我们研究了SR-BI特异性阻滞剂BLT-1对不同快速（、、）和慢速（和）复制球虫物种发育的影响。总体而言，BLT-1处理显著抑制了所有这些寄生虫的发育，表明在复制过程中存在一个与SR-BI相关的共同关键机制。然而，SR-BI基因转录不受和感染的影响。有趣的是，用BLT-1处理感染阶段会降低所有快速复制寄生虫的侵袭能力，同时细胞质钙水平持续升高。此外，BLT1介导的SR-BI阻断导致宿主细胞脂滴丰度和中性脂质含量增加，从而证实了该受体在一般脂质代谢中的重要性。最后，目前的数据表明SR-BI在成功的球虫感染中具有保守作用。
