ArticlePloS one2013
Toxoplasma gondii Proliferation Require Down-Regulation of Host Nox4 Expression via Activation of PI3 Kinase/Akt Signaling Pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
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- Ferroptosis modulation by Toxoplasma gondii suppresses sodium iodate-driven age-related macular degeneration.Genes & genomics · 2026Article
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- Toxoplasma gondii Induces Apoptosis via Endoplasmic Reticulum Stress-Derived Mitochondrial Pathway in Human Small Intestinal Epithelial Cell-Line.The Korean journal of parasitology · 2021Article
- FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth.Journal of cellular and molecular medicine · 2021Article
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- Melatonin Ameliorates Corticosterone-Mediated Oxidative Stress-Induced Colitis in Sleep-Deprived Mice Involving Gut Microbiota.Oxidative medicine and cellular longevity · 2021Article
- DNA double-strand breaks in the Toxoplasma gondii-infected cells by the action of reactive oxygen species.Parasites & vectors · 2020Article
- Effects of the PI3K/Akt signaling pathway on the apoptosis of early host cells infected with Eimeria tenella.Parasitology research · 2020Article
- The Role of PI3K/AKT Pathway and NADPH Oxidase 4 in Host ROS Manipulation by Toxoplasma gondii.The Korean journal of parasitology · 2020Article
- VEGF Production Is Regulated by the AKT/ERK1/2 Signaling Pathway and Controls the Proliferation ofFrontiers in cellular and infection microbiology · 2020Article
- The Cataleptic, Asymmetric, Analgesic, and Brain Biochemical Effects of Parkinson's Disease Can Be Affected byBioMed research international · 2020Article
- Silver Nanoparticle-Induced Apoptosis in ARPE-19 Cells Is Inhibited byInternational journal of nanomedicine · 2020Article
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- Disseminated and Congenital Toxoplasmosis in a Mother and Child With Activated PI3-Kinase δ Syndrome Type 2 (APDS2): Case Report and a Literature Review of Toxoplasma Infections in Primary Immunodeficiencies.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toxoplasma gondii results in ocular toxoplasmosis characterized by chorioretinitis with inflammation and necrosis of the neuroretina, pigment epithelium, and choroid. After invasion, T. gondii replicates in host cells before cell lysis, which releases the parasites to invade neighboring cells to repeat the life cycle and establish a chronic retinal infection. The mechanism by which T. gondii avoids innate immune defense, however, is unknown. Therefore, we determined whether PI3K/Akt signaling pathway activation by T. gondii is essential for subversion of host immunity and parasite proliferation. T. gondii infection or excretory/secretory protein (ESP) treatment of the human retinal pigment epithelium cell line ARPE-19 induced Akt phosphorylation, and PI3K inhibitors effectively reduced T. gondii proliferation in host cells. Furthermore, T. gondii reduced intracellular reactive oxygen species (ROS) while activating the PI3K/Akt signaling pathway. While searching for the main source of these ROS, we found that NADPH oxidase 4 (Nox4) was prominently expressed in ARPE-19 cells, and this expression was significantly reduced by T. gondii infection or ESP treatment along with decreased ROS levels. In addition, artificial reduction of host Nox4 levels with specific siRNA increased replication of intracellular T. gondii compared to controls. Interestingly, these T. gondii-induced effects were reversed by PI3K inhibitors, suggesting that activation of the PI3K/Akt signaling pathway is important for suppression of both Nox4 expression and ROS levels by T. gondii infection. These findings demonstrate that manipulation of the host PI3K/Akt signaling pathway and Nox4 gene expression is a novel mechanism involved in T. gondii survival and proliferation.
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