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トキソプラズマ原虫分泌蛋白質(PSP#7)の病原性における役割の解析

Research Project

Project/Area Number 13J01218
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Parasitology (including Sanitary zoology)
Research InstitutionOsaka University

Principal Investigator

馬 知秀  大阪大学, 医学系研究科, 特別研究員(DC2)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2014: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2013: ¥900,000 (Direct Cost: ¥900,000)
KeywordsToxoplasma gondii / NFAT4 / GRA6 / CAMLG / chemokine / Calcineurin
Outline of Annual Research Achievements

Toxoplasma gondii infection results in co-option and subversion of host cellular signaling pathways. This process involves discharge of T. gondii effector molecules from parasite secretory organelles such as rhoptries and dense granules. I found that the T. gondii polymorphic dense granule protein GRA6 regulates activation of the host transcription factor nuclear factor of activated T cells 4 (NFAT4). GRA6 overexpression robustly and selectively activated NFAT4 via calcium modulating ligand (CAMLG). Infection with wildtype (WT) but not GRA6-deficient parasites induced NFAT4 activation. Moreover, GRA6-deficient parasites failed to exhibit full virulence in local infection, and the treatment of WT mice with an NFAT inhibitor mitigated virulence of WT parasites. Notably, NFAT4-deficient mice displayed prolonged survival, decreased recruitment of CD11 b+ Ly6G+ cells to the site of infection, and impaired expression of chemokines such as Cxcl2 and Ccl2. In addition, infection with type I parasites culminated in significantly higher NFAT4 activation than type II parasites due to a polymorphism in the C terminus of GRA6. Collectively, these data suggest that GRA6-dependent NFAT4 activation is required for T. gondii manipulation of host immune responses to maximize the parasite virulence in a strain-dependent manner.

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (4 results)

All 2015 2014 2013

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (2 results)

  • [Journal Article] Role of Mouse and Human Autophagy Proteins in IFN-γ-Induced Cell-Autonomous Responses against Thxoplasma gondii2014

    • Author(s)
      Jun Ohshima, Youngae Lee, Miwa Sasai, Tatsuya Saitoh, Ji Su Ma, Naganori Kamiyama, Yoshiharu Matsuura, Suh Pann-Ghill, Mikako Hayashi, Shigeyuki Ebisu, Kiyoshi Takeda, Shizuo Akira, and Masahiro Yamamoto.
    • Journal Title

      The Journal of Immunology

      Volume: 192(7) Issue: 7 Pages: 3328-35

    • DOI

      10.4049/jimmunol.1302822

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA62014

    • Author(s)
      Ji Su Ma, Miwa Sasai, Jun Ohshima, Youngae Lee, Hironori Bando, Kiyoshi Takeda, and Masahiro Yamamoto
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 211 Issue: 10 Pages: 2013-2032

    • DOI

      10.1084/jem.20131272

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] トキソプラズマ原虫の多型濃縮顆粒タンパク質GRA6による選択的NFAT4の活性化について 口頭発表。2015

    • Author(s)
      Ji Su Ma
    • Organizer
      日本寄生虫学会大会
    • Place of Presentation
      杏林大学
    • Year and Date
      2015-03-21 – 2015-03-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Selective and strain-specific NFAT4 activation by the Tbxoplasma gondli2013

    • Author(s)
      馬 知秀
    • Organizer
      日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉)
    • Year and Date
      2013-12-13
    • Related Report
      2013 Annual Research Report

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Published: 2014-01-29   Modified: 2024-03-26  

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