PDF(Pubmed)
Abstract：
Toxoplasma gondii infects approximately one-third of the world\'s population resulting in a chronic infection with the parasite located in cysts in neurons in the brain. In most immunocompetent hosts the chronic infection is asymptomatic, but several studies have found correlations between Toxoplasma seropositivity and neuropsychiatric disorders, including Schizophrenia, and some other neurological disorders. Host-parasite interactions of bradyzoites in cysts in neurons is not well understood due in part to the lack of suitable in vitro human neuronal models. The advent of stem cell technologies in which human neurons can be derived in vitro from human induced pluripotent stem cells (hiPSCs) or direct conversion of somatic cells generating induced neurons (iNs), affords the opportunity to develop in vitro human neuronal culture systems to advance the understanding of T. gondii in human neurons. Human neurons derived from hiPSCs or iNs, generate pure human neuron monolayers that express differentiated neuronal characteristics. hiPSCs also generate 3D neuronal models that better recapitulate the cytoarchitecture of the human brain. In this review, an overview of iPSC-derived neurons and iN protocols leading to 2D human neuron cultures and hiPSC-derived 3D cerebral organoids will be given. The potential applications of these 2D and 3D human neuronal models to address questions about host-parasite interactions of T. gondii in neurons and the parasite in the CNS, will be discussed. These human neuronal in vitro models hold the promise to advance the understanding of T. gondii in human neurons and to improve the understanding of neuropathogenesis of chronic toxoplasmosis.
摘要：
弓形虫感染了世界上大约三分之一的人口，导致位于大脑神经元囊肿中的寄生虫慢性感染。在大多数有免疫能力的宿主中，慢性感染是无症状的，但是一些研究发现弓形虫血清阳性与神经精神疾病之间存在相关性，包括精神分裂症,和其他一些神经系统疾病。部分由于缺乏合适的体外人神经元模型，对神经元中囊肿中慢孢子的宿主-寄生虫相互作用尚未得到很好的理解。干细胞技术的出现，其中人类神经元可以在体外从人诱导多能干细胞（hiPSC）或直接转化体细胞产生诱导神经元（iN），提供了开发体外人类神经元培养系统的机会，以促进对人类神经元中弓形虫的理解。来自hiPSC或iNs的人神经元，生成表达分化神经元特征的纯人类神经元单层。hiPSC还生成3D神经元模型,其更好地概括人脑的细胞结构。在这次审查中,将概述iPSC衍生的神经元和导致2D人类神经元培养和hiPSC衍生的3D大脑类器官的iN方案。这些2D和3D人类神经元模型的潜在应用，以解决有关弓形虫在神经元中的宿主-寄生虫相互作用和中枢神经系统中的寄生虫的问题，将讨论。这些人类神经元体外模型有望促进对人类神经元中弓形虫的理解，并改善对慢性弓形虫病的神经发病机理的理解。
