Parasites, Hosts and Diseases

  • 제58권3호
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  • Pages.237-247
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  • 2020
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  • 2982-5164(pISSN)
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  • 1738-0006(eISSN)
대한기생충학·열대의학회 (The Korea Society for Parasitology and Tropical Medicine)
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The Role of PI3K/AKT Pathway and NADPH Oxidase 4 in Host ROS Manipulation by Toxoplasma gondii

  • Choi, Hei Gwon (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine) ;
  • Gao, Fei-Fei (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine) ;
  • Zhou, Wei (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine) ;
  • Sun, Pu-Reum (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine) ;
  • Yuk, Jae-Min (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine) ;
  • Lee, Young-Ha (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine) ;
  • Cha, Guang-Ho (Department of Medical Science & Infection Biology, Chungnam National University, School of Medicine)
  • 투고 : 2020.01.02
  • 심사 : 2020.05.27
  • 발행 : 2020.06.30
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초록

Dendritic cell is one of the first innate immune cell to encounter T. gondii after the parasite crosses the host intestinal epithelium. T. gondii requires intact DC as a carrier to infiltrate into host central nervous system (CNS) without being detected or eliminated by host defense system. The mechanism by which T. gondii avoids innate immune defense of host cell, especially in the dendritic cell is unknown. Therefore, we examined the role of host PI3K/AKT signaling pathway activation by T. gondii in dendritic cell. T. gondii infection or T. gondii excretory/secretory antigen (TgESA) treatment to the murine dendritic cell line DC2.4 induced AKT phosphorylation, and treatment of PI3K inhibitors effectively suppressed the T. gondii proliferation but had no effect on infection rate or invasion rate. Furthermore, it is found that T. gondii or TgESA can reduce H2O2-induced intracellular reactive oxygen species (ROS) as well as host endogenous ROS via PI3K/AKT pathway activation. While searching for the main source of the ROS, we found that NADPH oxidase 4 (NOX4) expression was controlled by T. gondii infection or TgESA treatment, which is in correlation with previous observation of the ROS reduction by identical treatments. These findings suggest that the manipulation of the host PI3K/AKT signaling pathway and NOX4 expression is an essential mechanism for the down-regulation of ROS, and therefore, for the survival and the proliferation of T. gondii.

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참고문헌

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피인용 문헌

  1. FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth vol.25, pp.19, 2020, https://doi.org/10.1111/jcmm.16889