Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
Mol Microbiol. 2021 May;115(5):839-848. doi: 10.1111/mmi.14634. Epub 2020 Nov 21.
The intracellular parasite Toxoplasma gondii infects nucleated cells in virtually all warm-blooded vertebrates, including one-third of the human population. While immunocompetent hosts do not typically show symptoms of acute infection, parasites are retained in latent tissue cysts that can be reactivated upon immune suppression, potentially damaging key organ systems. Toxoplasma has a multistage life cycle that is intimately linked to environmental stresses and host signals. As this protozoan pathogen is transmitted between multiple hosts and tissues, it evaluates these external signals to appropriately differentiate into distinct life cycle stages, such as the transition from its replicative stage (tachyzoite) to the latent stage (bradyzoite) that persists as tissue cysts. Additionally, in the gut of its definitive host, felines, Toxoplasma converts into gametocytes that produce infectious oocysts (sporozoites) that are expelled into the environment. In this review, we highlight recent advances that have illuminated the interfaces between Toxoplasma and host and how these interactions control parasite stage conversion. Mechanisms underlying these stage transitions are important targets for therapeutic intervention aimed at thwarting parasite transmission and pathogenesis.
细胞内寄生虫刚地弓形虫感染几乎所有温血脊椎动物的有核细胞,包括三分之一的人类。虽然免疫功能正常的宿主通常不会出现急性感染的症状,但寄生虫会被保留在潜伏的组织囊肿中,当免疫抑制时可能会被重新激活,从而损害关键的器官系统。刚地弓形虫具有多阶段的生命周期,与环境压力和宿主信号密切相关。由于这种原生动物病原体在多个宿主和组织之间传播,它会评估这些外部信号,以适当分化为不同的生命周期阶段,例如从其复制阶段(速殖子)到潜伏阶段(缓殖子),后者以组织囊肿的形式存在。此外,在其终末宿主猫的肠道中,刚地弓形虫转化为配子体,产生具有感染性的卵囊(孢子囊),被排出到环境中。在这篇综述中,我们强调了最近的进展,这些进展阐明了弓形虫与宿主之间的界面以及这些相互作用如何控制寄生虫阶段转换。这些阶段转变的机制是针对阻止寄生虫传播和发病机制的治疗干预的重要目标。