J Clin Invest. 2020 Jul 1;130(7):3370-3380. doi: 10.1172/JCI136226.
Toxoplasma gondii is an incredibly successful parasite owing in part to its ability to persist within cells for the life of the host. Remarkably, at least 350 host species of T. gondii have been described to date, and it is estimated that 30% of the global human population is chronically infected. The importance of T. gondii in human health was made clear with the first reports of congenital toxoplasmosis in the 1940s. However, the AIDS crisis in the 1980s revealed the prevalence of chronic infection, as patients presented with reactivated chronic toxoplasmosis, underscoring the importance of an intact immune system for parasite control. In the last 40 years, there has been tremendous progress toward understanding the biology of T. gondii infection using rodent models, human cell experimental systems, and clinical data. However, there are still major holes in our understanding of T. gondii biology, including the genes controlling parasite development, the mechanisms of cell-intrinsic immunity to T. gondii in the brain and muscle, and the long-term effects of infection on host homeostasis. The need to better understand the biology of chronic infection is underscored by the recent rise in ocular disease associated with emerging haplotypes of T. gondii and our lack of effective treatments to sterilize chronic infection. This Review discusses the cell types and molecular mediators, both host and parasite, that facilitate persistent T. gondii infection. We highlight the consequences of chronic infection for tissue-specific pathology and identify open questions in this area of host-Toxoplasma interactions.
刚地弓形虫是一种非常成功的寄生虫，部分原因是它能够在宿主的一生中存在于细胞内。值得注意的是，迄今为止已经描述了至少 350 种宿主物种的刚地弓形虫，据估计全球有 30%的人口患有慢性感染。20 世纪 40 年代首次报道先天性弓形虫病，这清楚地表明了刚地弓形虫在人类健康中的重要性。然而，20 世纪 80 年代的艾滋病危机揭示了慢性感染的流行，因为患者出现了慢性弓形虫病的再激活，这突显了完整的免疫系统对寄生虫控制的重要性。在过去的 40 年中，利用啮齿动物模型、人类细胞实验系统和临床数据，在理解刚地弓形虫感染的生物学方面取得了巨大进展。然而，我们对刚地弓形虫生物学的理解仍然存在重大空白，包括控制寄生虫发育的基因、大脑和肌肉中针对刚地弓形虫的细胞内固有免疫机制，以及感染对宿主内稳态的长期影响。最近与刚地弓形虫新出现的单倍型相关的眼部疾病的增加，以及我们缺乏有效的方法来消除慢性感染，突显了更好地理解慢性感染生物学的必要性。这篇综述讨论了促进刚地弓形虫持续感染的细胞类型和分子介质，包括宿主和寄生虫。我们强调了慢性感染对组织特异性病理学的后果，并确定了宿主-刚地弓形虫相互作用这一领域的开放性问题。
