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Evaluation of molecular mechanism modulating stage conversion of Toxoplasma gondii by using primary culuter neuron

Research Project

Project/Area Number 18K14577
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionObihiro University of Agriculture and Veterinary Medicine

Principal Investigator

Ihara Fumiaki  帯広畜産大学, 原虫病研究センター, 特任研究員 (00800773)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsトキソプラズマ / トランスクリプトーム解析 / ブラディゾイト / 初代培養神経細胞 / 慢性感染 / ステージ転換 / 神経細胞 / 潜伏機構 / Toxoplasma gondii / CRISPR/Cas9
Outline of Final Research Achievements

In this study, we focused on the stage conversion between tachyzoites and bradyzoites of Toxoplasma gondii that spontaneously occurred in particular cells such as nerve cells, and aimed to elucidate the mechanism of chronic infection with T. gondii that formed unremovable tissue cyst in the host’s brain. We have succeeded in establishing an experiment to evaluate stage conversion efficiency in primary cultured neurons. A combination analysis of this assay and four gene-deficient parasites prepared showed no responsibility to the stage conversion. On the other hand, one of these deficient parasites was highly virulent to mice. Our results indicate that understanding the function of this gene will provide insight to a new molecular mechanism involved in the pathophysiology of toxoplasmosis.

Academic Significance and Societal Importance of the Research Achievements

増殖型虫体から潜伏型虫体へのステージ転換は、トキソプラズマの生存戦略および病態に深く関わる現象であり、その分子機構を明らかとすることはトキソプラズマ研究の中でも中心的課題の1つとなっている。これまで、その簡便さから人為的な刺激を加えて誘導するステージ転換モデルによる研究が数多くなされてきた反面、生体内でのステージ転換の仕組みはほとんど不明なままであった。本研究において、主要な潜伏先細胞である神経細胞を使ったモデルを構築し、ステージ転換能率を定量的に評価可能であることが示された。このことで、より生体内の環境に近いモデルを使ったステージ転換機構の研究の発展につながることが期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Toxoplasma gondii dense granule proteins 7, 14, and 15 are involved in modification and control of the immune response mediated via NF-κB pathway2020

    • Author(s)
      Fumiaki Ihara, Ragab M Fereig, Yuu Himori, Kyohko Kameyama, Kosuke Umeda, Sachi Tanaka, Rina Ikeda, Masahiro Yamamoto, Yoshifumi Nishikawa
    • Journal Title

      Frontiers in Immunology

      Volume: 未定

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of Toll-like receptor 2 in the cerebral immune response and behavioral changes caused by latent Toxoplasma infection in mice2019

    • Author(s)
      Fumiaki Ihara, Sachi Tanaka, Ragab M Fereig, Maki Nishimura, Yoshifumi Nishikawa
    • Journal Title

      PloS One

      Volume: 14 Issue: 8 Pages: e0220560-e0220560

    • DOI

      10.1371/journal.pone.0220560

    • NAID

      120006732638

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Toxoplasma gondii conducts NFκB pathway of host cells, dense granule protein 14 is a novel member of the orchestra2019

    • Author(s)
      Fumiaki Ihara, Kosuke Umeda, Masahiro Yamamoto, Yoshifumi Nishikawa
    • Organizer
      あわじ感染と免疫フォーラム
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Toxoplasma gondii dense granule protein 14はNFκB経路を介した宿主免疫応答の制御に関与する2019

    • Author(s)
      猪原 史成
    • Organizer
      第88回日本寄生虫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Toxoplasma gondii dense granule protein 14 は宿主細胞のNFκB経路を制御し宿主の免疫応答を調節する2018

    • Author(s)
      猪原 史成、西川義文
    • Organizer
      第161回日本獣医学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Toxoplasma gondii dense granule protein 14 は宿主細胞のNFκB経路を制御し宿主の免疫応答を調節する2018

    • Author(s)
      猪原 史成、西川義文
    • Organizer
      第26回分子寄生虫学ワークショップおよび第15回分子寄生虫・マラリア研究フォーラム合同大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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