2014 Fiscal Year Annual Research Report
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
| Project/Area Number |
13J01218
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| Research Institution | Osaka University |
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Principal Investigator |
馬 知秀 大阪大学, 医学系研究科, 特別研究員(DC2)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | Toxoplasma gondii / NFAT4 / GRA6 / CAMLG / chemokine |
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| 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.
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| Research Progress Status |
26年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
26年度が最終年度であるため、記入しない。
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[Journal Article] Role of Mouse and Human Autophagy Proteins in IFN-γ-Induced Cell-Autonomous Responses against Toxoplasma 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
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Journal Title
The Journal of Immunology
Volume: 192(7)
Pages: 3328-35
DOI
Peer Reviewed
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