Modelling Toxoplasma gondii infection in human cerebral organoids.
Modelling Toxoplasma gondii infection in human cerebral organoids.
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DOI：
10.1080/22221751.2020.1812435
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发表时间：
2020-12
影响因子：
13.2
通讯作者：
Kim JH
中科院分区：
文献类型：
--
作者：
Seo HH;Han HW;Lee SE;Hong SH;Cho SH;Kim SC;Koo SK;Kim JH
多能干细胞衍生的脑类器官具有重现体内人脑组织的病理生理学的潜力，构成了用于建模脑疾病（包括传染病）的宝贵资源。弓形虫是一种细胞内的原生寄生虫，感染包括人类在内的大多数温血动物，引起弓形虫病。在免疫缺陷患者和孕妇中，感染通常导致严重的中枢神经系统疾病和胎儿流产。然而，由于有限的体外模型系统，理解疾病的分子病理生理学一直具有挑战性。本研究建立了一种新的T.利用人脑类器官感染弓形虫我们观察到速殖子可以感染人脑类器官，并转化为缓殖子，在寄生空泡中复制形成包囊，表明T。在脑类器官中有效地模拟了弓形虫无性生活周期。T.感染了弓形虫的类器官揭示了针对感染的I型干扰素免疫应答的激活。此外，在脑类器官中，T.弓形虫表现出与原生动物入侵和复制相关的改变的转录组。这项研究表明，脑类器官作为生理相关的体外模型系统，有助于促进对T。弓形虫感染和宿主相互作用。
Pluripotent stem cell-derived cerebral organoids have the potential to recapitulate the pathophysiology of in vivo human brain tissue, constituting a valuable resource for modelling brain disorders, including infectious diseases. Toxoplasma gondii, an intracellular protozoan parasite, infects most warm-blooded animals, including humans, causing toxoplasmosis. In immunodeficient patients and pregnant women, infection often results in severe central nervous system disease and fetal miscarriage. However, understanding the molecular pathophysiology of the disease has been challenging due to limited in vitro model systems. Here, we developed a new in vitro model system of T. gondii infection using human brain organoids. We observed that tachyzoites can infect human cerebral organoids and are transformed to bradyzoites and replicate in parasitophorous vacuoles to form cysts, indicating that the T. gondii asexual life cycle is efficiently simulated in the brain organoids. Transcriptomic analysis of T. gondii-infected organoids revealed the activation of the type I interferon immune response against infection. In addition, in brain organoids, T. gondii exhibited a changed transcriptome related to protozoan invasion and replication. This study shows cerebral organoids as physiologically relevant in vitro model systems useful for advancing the understanding of T. gondii infections and host interactions.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1097/00005072-199611000-00006
发表时间：
1996-11-01
影响因子：
3.2
作者：
Halonen, SK;Lyman, WD;Chiu, FC
通讯作者：
Chiu, FC
影响因子：
3.4
作者：
Mahmoud, Motamed Elsayed;Ui, Fumiki;Nishikawa, Yoshifumi
通讯作者：
Nishikawa, Yoshifumi
影响因子：
5.8
作者：
Da Gama, LM;Ribeiro-Gomes, FL;Arnholdt, ACV
通讯作者：
Arnholdt, ACV
影响因子：
3.7
作者：
Danielson, Jeffrey J.;Perez, Nicolas;Coppens, Isabelle
通讯作者：
Coppens, Isabelle