title: Use of human induced pluripotent stem cell-derived neurons as a model for Cerebral Toxoplasmosis.
abstract: Toxoplasma gondii is a ubiquitous protozoan parasite with approximately one-third of the worlds' population chronically infected. In chronically infected individuals, the parasite resides primarily in cysts within neurons in the central nervous system. The chronic infection in immunocompetent individuals has been considered to be asymptomatic but increasing evidence indicates the chronic infection can lead to neuropsychiatric disorders such as Schizophrenia, prenatal depression and suicidal thoughts. A better understanding of the mechanism(s) by which the parasite exerts effects on human behavior is limited due to lack of suitable human neuronal models. In this paper, we report the use of human neurons derived from normal cord blood CD34+ cells generated via genetic reprogramming, as an in vitro model for the study T. gondii in neurons. This culture method resulted in a relatively pure monolayer of induced human neuronal-like cells that stained positive for neuronal markers, MAP2, NFL, NFH and NeuN. These induced human neuronal-like cells (iHNs) were efficiently infected by the Prugniad strain of the parasite and supported replication of the tachyzoite stage and development of the cyst stage. Infected iHNs could be maintained through 5 days of infection, allowing for formation of large cysts. This induced human neuronal model represents a novel culture method to study both tachyzoite and bradyzoite stages of T. gondii in human neurons.
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA.
authors.forename: Danah
authors.initials: D
authors.lastname: Ashour
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Dratz
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA. Electronic address: shalonen@montana.edu.
authors.forename: Sandra
authors.initials: S
authors.lastname: Halonen
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D008954:Models, Biological; D008962:Models, Theoretical; D009474:Neurons / Q000382:microbiology* / Q000473:pathology*; D016781:Toxoplasmosis, Cerebral / Q000382:microbiology* / Q000473:pathology*
keywords: Cysts; Induced neuronal cells; Latent toxoplasmosis