z-logo
open-access-imgOpen Access
FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth
Author(s) -
Gao FeiFei,
Quan JuanHua,
Choi InWook,
Lee YeonJae,
Jang SeulGi,
Yuk JaeMin,
Lee YoungHa,
Cha GuangHo
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16889
Subject(s) - toxoplasma gondii , downregulation and upregulation , parasite hosting , mobilization , irf3 , host (biology) , protozoan parasite , virology , biology , microbiology and biotechnology , immunology , immune system , political science , innate immune system , computer science , gene , genetics , antibody , world wide web , law
Fas‐associated factor 1 (FAF1) has gained a reputation as a member of the FAS death‐inducing signalling complex. 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‐19 cells, FAF1 expression level was downregulated by Toxoplasma gondii infection, and PI3K/AKT inhibitors reversed T .  gondii ‐induced 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 T .  gondii is correlated with enhanced IRF3 transcription activity. Inhibition of PI3K/AKT pathway with specific inhibitors had no effect on the level of T .  gondii ‐induced IRF3 phosphorylation but blocked IRF3 nuclear import and ISGs transcription. These results suggest that T .  gondii can downregulate host FAF1 in PI3K/AKT/FOXO1‐dependent manner, and the event is essential for IRF3 nuclear translocation to active the transcription of ISGs and thereby T .  gondii proliferation.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here