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However, the role of FAF1 in the immunity response is not fully understood. Here, we report that, in the human retinal pigment epithelial (RPE) cell line ARPE\u201019 cells, FAF1 expression level was downregulated by <jats:italic>Toxoplasma gondii<\/jats:italic> infection, and PI3K\/AKT inhibitors reversed <jats:italic>T<\/jats:italic>.<jats:italic>\u00a0gondii<\/jats:italic>\u2010induced FAF1 downregulation. In silico analysis for the FAF1 promoter sequence showed the presence of a FOXO response element (FRE), which is a conserved binding site for FOXO1 transcription factor. In accordance with the finding, FOXO1 overexpression potentiated, whereas FOXO1 depletion inhibited intracellular FAF1 expression level. We also found that FAF1 downregulation by <jats:italic>T<\/jats:italic>.<jats:italic>\u00a0gondii<\/jats:italic> is correlated with enhanced IRF3 transcription activity. Inhibition of PI3K\/AKT pathway with specific inhibitors had no effect on the level of <jats:italic>T<\/jats:italic>.<jats:italic>\u00a0gondii<\/jats:italic>\u2010induced IRF3 phosphorylation but blocked IRF3 nuclear import and ISGs transcription. These results suggest that <jats:italic>T<\/jats:italic>.<jats:italic>\u00a0gondii<\/jats:italic> can downregulate host FAF1 in PI3K\/AKT\/FOXO1\u2010dependent manner, and the event is essential for IRF3 nuclear translocation to active the transcription of ISGs and thereby <jats:italic>T<\/jats:italic>.<jats:italic>\u00a0gondii<\/jats:italic> proliferation.<\/jats:p>","DOI":"10.1111\/jcmm.16889","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T18:16:07Z","timestamp":1630433767000},"page":"9460-9472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["FAF1 downregulation by <i>Toxoplasma gondii<\/i> enables host IRF3 mobilization and promotes parasite growth"],"prefix":"10.1111","volume":"25","author":[{"given":"Fei\u2010Fei","family":"Gao","sequence":"first","affiliation":[{"name":"Brain Korea 21 FOUR Project for Medical Science Chungnam National University Daejeon 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