开发一个异位人肝模型用于恶性疟原虫肝阶段感染。
Development of an ectopic huLiver model for Plasmodium liver stage infection.
发表日期:2023
作者:
Gabriela Samayoa-Reyes, Siobhan M Flaherty, Kristina S Wickham, Sara Viera-Morilla, Pamela M Strauch, Alison Roth, Laura Padrón, Conner M Jackson, Patricia Meireles, David Calvo, Wanlapa Roobsoong, Niwat Kangwanrangsan, Jetsumon Sattabongkot, Gregory Reichard, Maria José Lafuente-Monasterio, Rosemary Rochford
来源:
Parasites & Vectors
摘要:
早期疟原虫感染需要在宿主肝细胞中进行寄生虫复制,称为肝阶段(LS)。然而,由于物种特异性挑战,对人类LS感染动力学的认识有限。在这里报告的是一种可重复、易于操作且成本适中的体内模型,用于研究小鼠中人类疟原虫LS;异位huLiver模型。通过皮下注射HC-04细胞系生成异位huLiver肿瘤,并表明它们可以被新鲜解剖的孢子虫和感染蚊子咬伤的孢子虫感染。种植有人类红细胞的小鼠中的过渡到血液阶段感染的证据支持完全LS发育的存在。此外,这个模型成功地评估了它在测试抗疟疾药物方面的实用性,如青蒿素被证明是针对恶性疟原虫的因果预防药。这里提供了一种新平台,用于研究人类疟原虫感染,有助于药物发现。版权:这是一个完全免费、无版权的开放获取文章,可以自由地被任何人复制、分发、传播、修改、构建或以任何合法目的使用。该作品根据创意共享CC0公共领域奉献提供。
Early Plasmodium falciparum and P. vivax infection requires parasite replication within host hepatocytes, referred to as liver stage (LS). However, limited understanding of infection dynamics in human LS exists due to species-specificity challenges. Reported here is a reproducible, easy-to-manipulate, and moderate-cost in vivo model to study human Plasmodium LS in mice; the ectopic huLiver model. Ectopic huLiver tumors were generated through subcutaneous injection of the HC-04 cell line and shown to be infectible by both freshly dissected sporozoites and through the bite of infected mosquitoes. Evidence for complete LS development was supported by the transition to blood-stage infection in mice engrafted with human erythrocytes. Additionally, this model was successfully evaluated for its utility in testing antimalarial therapeutics, as supported by primaquine acting as a causal prophylactic against P. falciparum. Presented here is a new platform for the study of human Plasmodium infection with the potential to aid in drug discovery.Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.