Dalapati Trisha, Moore Julie M
Duke University School of Medicine, Duke University, Durham, NC, USA.
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Curr Clin Microbiol Rep. 2021 Jun;8(2):87-102. doi: 10.1007/s40588-021-00166-8. Epub 2021 Apr 11.
Malaria is a disease caused by parasites that reside in host red blood cells and use hemoglobin as a nutrient source. Heme released by hemoglobin catabolism is modified by the parasite to produce hemozoin (HZ), which has toxic effects on the host. Experimentation aiming to elucidate how HZ contributes to malaria pathogenesis has utilized different preparations of this molecule, complicating interpretation and comparison of findings. We examine natural synthesis and isolation of HZ and highlight studies that have used multiple preparations, including synthetic forms, in a comparative fashion.
Recent work utilizing sophisticated imaging and detection techniques reveals important molecular characteristics of HZ synthesis and biochemistry. Other recent studies further refine understanding of contributions of HZ to malaria pathogenesis yet highlight the continuing need to characterize HZ preparations and contextualize experimental conditions in the in vivo infection milieu.
This review highlights the necessity of collectively determining what is physiologically relevant HZ. Characterization of isolated natural HZ and use of multiple preparations in each study are recommended with application of in vivo studies whenever possible. Adoption of such practices is expected to improve reproducibility of results and elucidate the myriad of ways that HZ participates in malaria pathogenesis.
疟疾是一种由寄生于宿主红细胞并以血红蛋白为营养源的寄生虫引起的疾病。血红蛋白分解代谢释放的血红素被寄生虫修饰以产生疟色素(HZ),其对宿主具有毒性作用。旨在阐明HZ如何促成疟疾发病机制的实验使用了该分子的不同制剂,这使得研究结果的解释和比较变得复杂。我们研究了HZ的天然合成和分离,并重点介绍了以比较方式使用多种制剂(包括合成形式)的研究。
最近利用先进成像和检测技术开展的研究揭示了HZ合成和生物化学的重要分子特征。其他近期研究进一步细化了对HZ在疟疾发病机制中作用的理解,但也强调了持续需要对HZ制剂进行表征,并将实验条件与体内感染环境相结合。
本综述强调了共同确定生理相关HZ的必要性。建议对分离出的天然HZ进行表征,并在每项研究中使用多种制剂,尽可能开展体内研究。采用这些做法有望提高结果的可重复性,并阐明HZ参与疟疾发病机制的多种方式。