CCAAT/Enhancer-Binding Protein Mediates the Killing of Toxoplasma gondii by Inducing Autophagy in Nonhematopoietic Cells

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 (C/EBP ) is associated with the regulation of autophagy. Herein, we hypothesized that C/EBP plays roles in inducing autophagy in nonhematopoietic cells. Expression of C/EBP was aberrantly regulated in endothelial cells and retinal pigment epithelial cells challenged by T. gondii. Inhibition of C/EBP reduced the killing of T. gondii in nonhematopoietic cells, whereas C/EBP 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 overexpression, but increased by C/EBP inhibition. The increase in T. gondii killing induced by C/EBP overexpression was blocked by the mTOR activator phosphatidic acid and was increased by the inhibitor AZD8055. In conclusion, we demonstrate that C/EBP expression is increased in nonhematopoietic cells infected by T. gondii, resulting in the activation of autophagy in host cells by inhibiting mTOR pathway.