トキソプラズマ原虫に対する宿主免疫系におけるIRGB6の役割の解明

• Project/Area Number: 18K05970
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Osaka University
• Principal Investigator: 李 英愛 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (60610681)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Discontinued (Fiscal Year 2019)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Irgb6 / Toxoplasma gondii / Ubiquitination / Pphospholipid / IFN誘導性GTPase / トキソプラズマ / 寄生胞 / 人畜共通感染症 / インターフェロン

Outline of Annual Research Achievements

We characterized the role of IFN-γ-inducible immunity-related GTPase Irgb6 in the cell-autonomous response against Toxoplasma gondii (T. gondii), which involves vacuole ubiquitination and breakdown. We show that Irgb6 is capable of binding a specific phospholipid on the parasitophorous vacuole (PV)membrane. Furthermore, the absence of Irgb6 causes reduced targeting of other effector IRG proteins to the PV. This suggests that Irgb6 has a role as a pioneer in the process by which multiple IRG proteins access the PV.

Research Products

• [Journal Article] Initial phospholipid-dependent Irgb6 targeting to Toxoplasma gondii vacuoles mediates host defense. (2019)
  • Author(s): Lee, Y., Yamada, H., Pradipta, A., Ma, J.S., Okamoto, M., Nagaoka, H., Takashima, E., Standley, D.M., Sasai, M., Takei, K., Yamamoto, M.
  • Journal Title: Life Science Alliance Volume: 3 Issue: 1 Pages: 000-000
  • DOI: 10.26508/lsa.201900549
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inducible Nitric Oxide Synthase Is a Key Host Factor for Toxoplasma GRA15-Dependent Disruption of the Gamma Interferon-Induced Antiparasitic Human Response (2018)
  • Author(s): Bando Hironori、Lee Youngae、Sakaguchi Naoya、Pradipta Ariel、Ma Ji Su、Tanaka Shun、Cai Yihong、Liu Jianfa、Shen Jilong、Nishikawa Yoshifumi、Sasai Miwa、Yamamoto Masahiro
  • Journal Title: mBio Volume: 9 Issue: 5 Pages: 5-5
  • DOI: 10.1128/mbio.01738-18
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Toxoplasma Effector TgIST Targets Host IDO1 to Antagonize the IFN-γ-Induced Anti-parasitic Response in Human Cells (2018)
  • Author(s): Bando Hironori、Sakaguchi Naoya、Lee Youngae、Pradipta Ariel、Ma Ji Su、Tanaka Shun、Lai De-Hua、Liu Jianfa、Lun Zhao-Rong、Nishikawa Yoshifumi、Sasai Miwa、Yamamoto Masahiro
  • Journal Title: Frontiers in Immunology Volume: 9 Pages: 2073-2073
  • DOI: 10.3389/fimmu.2018.02073
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] An effector IRG is a critical factor mediating interferon-g-induced ubiquitin decoration of Toxoplasma gondii parasitophorous vacuoles (2019)
  • Author(s): Youngae Lee
  • Organizer: Parasite-Immunology conference