title: Neurons are the Primary Target Cell for the Brain-Tropic Intracellular Parasite Toxoplasma gondii.
abstract: Toxoplasma gondii, a common brain-tropic parasite, is capable of infecting most nucleated cells, including astrocytes and neurons, in vitro. Yet, in vivo, Toxoplasma is primarily found in neurons. In vitro data showing that interferon-γ-stimulated astrocytes, but not neurons, clear intracellular parasites suggest that neurons alone are persistently infected in vivo because they lack the ability to clear intracellular parasites. Here we test this theory by using a novel Toxoplasma-mouse model capable of marking and tracking host cells that directly interact with parasites, even if the interaction is transient. Remarkably, we find that Toxoplasma shows a strong predilection for interacting with neurons throughout CNS infection. This predilection remains in the setting of IFN-γ depletion; infection with parasites resistant to the major mechanism by which murine astrocytes clear parasites; or when directly injecting parasites into the brain. These findings, in combination with prior work, strongly suggest that neurons are not incidentally infected, but rather they are Toxoplasma's primary in vivo target.
authors.affiliation: BIO5 Institute, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Carla M
authors.initials: CM
authors.lastname: Cabral
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Tuladhar
authors.affiliation: BIO5 Institute, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Hans K
authors.initials: HK
authors.lastname: Dietrich
authors.affiliation: BIO5 Institute, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nguyen
authors.affiliation: Undergraduate Biology Research Program, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Wes R
authors.initials: WR
authors.lastname: MacDonald
authors.affiliation: BIO5 Institute, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Tapasya
authors.initials: T
authors.lastname: Trivedi
authors.affiliation: BIO5 Institute, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Asha
authors.initials: A
authors.lastname: Devineni
authors.affiliation: BIO5 Institute, University of Arizona, Tucson, Arizona, United States of America.|Department of Immunobiology, University of Arizona, Tucson, Arizona, United States of America.|Department of Neurology, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Anita A
authors.initials: AA
authors.lastname: Koshy
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000469:parasitology*; D001921:Brain / Q000469:parasitology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000378:metabolism; D042541:Intracellular Space / Q000469:parasitology; D051379:Mice; D009474:Neurons / Q000469:parasitology*; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000469:parasitology*
chemical_list: D007371:Interferon-gamma