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大学・研究所にある論文を検索できる 「Toxoplasma Gondii Effectors TgIST and TgGRA15 Differentially Target Host IDO1 to Antagonize the IFN-γ-induced Anti-T. Gondii Response in Human Cells」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
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Toxoplasma Gondii Effectors TgIST and TgGRA15 Differentially Target Host IDO1 to Antagonize the IFN-γ-induced Anti-T. Gondii Response in Human Cells

BANDO Hironori FUKUDA Yasuhiro YAMAMOTO Masahiro KATO Kentaro 東北大学

2020.03

概要

Toxoplasma is an important intracellular pathogen that causes lethal toxoplasmosis in humans and animals. Interferon-γ (IFN-γ) is critical for anti-T. gondii responses in both humans and mice. Recent extensive studies using the mouse as a model organism have revealed that IFN-γ-inducible GTPases play critical roles and have revealed that virulent T. gondii can inhibit IFN-γ-mediated host immune responses. Thus, the relationship between host immunity and T. gondii virulence is well established in mice. In contrast, IFN-γ-induced anti-T. gondii responses in humans are not completely clear because the IFN-γ-inducible GTPase-mediated anti-T. gondii responses may not be notable in humans. Therefore, the T. gondii virulence strategy to resist IFN-γ-induced anti-T. gondii responses in humans also remains largely unclear. Here, we generated human cells lacking the IFN-γ-inducible gene, and showed that IDO1 is required for the IFN-γ-induced response in human cells. Then, we focused on T. gondii virulence mechanisms in human cells. Specifically, we focused on the distinct T. gondii virulence mechanisms involving TgIST and TgGRA15 to suppress IFN-γ-dependent immunity in human cells. We generated TgIST- or TgGRA15- deficient T. gondii by using the CRISPR/Cas9 system, and showed that IDO1 mRNA induction is inhibited in a TgIST-dependent manner in IFN-γ-stimulated human cells. We also found that the IDO1-dependent anti-T. gondii response is inhibited in a TgGRA15-dependent manner in secondarily infected cells. Taken together, our data show that T. gondii possesses at least two differential virulence mechanisms in which IDO1 is targeted by TgIST and TgGRA15 to antagonize IFN-γ-induced anti-T. gondii responses in human cells.

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