Modelling Toxoplasma gondii infection in human cerebral organoids.
Hyang-Hee SeoHyo-Won HanSang-Eun LeeSung-Hee HongShin-Hyeong ChoSang Cheol KimSoo Kyung KooJung-Hyun KimPublished in: Emerging microbes & infections (2021)
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.
Keyphrases
- toxoplasma gondii
- induced pluripotent stem cells
- pregnant women
- cerebral ischemia
- subarachnoid hemorrhage
- endothelial cells
- immune response
- end stage renal disease
- single cell
- white matter
- infectious diseases
- resting state
- chronic kidney disease
- gene expression
- newly diagnosed
- ejection fraction
- rna seq
- multiple sclerosis
- brain injury
- peritoneal dialysis
- toll like receptor
- risk assessment
- climate change
- patient reported outcomes