title: CCAAT/Enhancer-Binding Protein β Mediates the Killing of Toxoplasma gondii by Inducing Autophagy in Nonhematopoietic Cells.
abstract: Autophagy is a main defense strategy by which infected host cells can virtually induce the killing of parasite, including Toxoplasma gondii. However, the regulatory mechanisms of autophagy in T. gondii-infected nonhematopoietic cells are still unknown. Emerging evidence indicates that CCAAT/enhancer-binding protein β (C/EBP β) is associated with the regulation of autophagy. Herein, we hypothesized that C/EBP β plays roles in inducing autophagy in nonhematopoietic cells. Expression of C/EBP β was aberrantly regulated in endothelial cells and retinal pigment epithelial cells challenged by T. gondii. Inhibition of C/EBP β reduced the killing of T. gondii in nonhematopoietic cells, whereas C/EBP β overexpression resulted in the enhancement of killing of T. gondii as well as the increase in autophagy in infected cells. Furthermore, the mammalian target of rapamycin (mTOR) activation was found to be reduced by C/EBP β overexpression, but increased by C/EBP β inhibition. The increase in T. gondii killing induced by C/EBP β overexpression was blocked by the mTOR activator phosphatidic acid and was increased by the inhibitor AZD8055. In conclusion, we demonstrate that C/EBP β expression is increased in nonhematopoietic cells infected by T. gondii, resulting in the activation of autophagy in host cells by inhibiting mTOR pathway.
authors.affiliation: 1 College of Basic Medicine Sciences, Jilin University , Changchun, China .
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 2 Laboratory Animal Center of North China University of Science and Technology , Tangshan, China .
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: 3 School of Basic Medical Sciences, Fourth Military Medical University , Xian, China .
authors.forename: Jiaqi
authors.initials: J
authors.lastname: An
authors.affiliation: 4 College of Veterinary Medicine, Jilin University , Changchun, China .
authors.forename: Xichen
authors.initials: X
authors.lastname: Zhang
mesh_terms: D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000469:parasitology*; D015870:Gene Expression; D006790:Host-Parasite Interactions / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000494:pharmacology; D034622:RNA Interference; D055213:Retinal Pigment Epithelium / Q000166:cytology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014122:Toxoplasma / Q000502:physiology*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D009025:Morpholines; D010712:Phosphatidic Acids; C546624:(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol; D058570:TOR Serine-Threonine Kinases
keywords: C/EBP β; T. gondii; autophagy; killing; mTOR; nonhematopoietic cells