Development of the highly efficient Toxoplasma anti-tumor vaccine

• Project/Area Number: 15K15122
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Osaka University
• Principal Investigator: Yamamoto Masahiro 大阪大学, 微生物病研究所, 教授 (00444521)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: トキソプラズマ / キラーT細胞 / RabGDIa / GBP2 / 抗原提示

Outline of Final Research Achievements

Here we show that interferon γ (IFN-γ) stimulates ubiquitin and p62 recruitment to T. gondii parasitophorous vacuoles (PVs). Some essential autophagy-related proteins, but not all, are required for this recruitment. Regardless of normal IFN-γ-induced T. gondii clearance activity and ubiquitination, p62 deficiency in antigen-presenting cells (APCs) and mice diminishes the robust IFN-γ-primed activation of CD8(+) T cells that recognize the T. gondii-derived antigen secreted into PVs. Because the expression of Atg3 and Irgm1/m3 in APCs is essential for PV disruption, ubiquitin and p62 recruitment, and vacuolar-antigen-specific CD8(+) T cell activation, IFN-γ-mediated ubiquitination and the subsequent recruitment of p62 to T. gondii are specifically required for the acquired immune response after PV disruption by IFN-γ-inducible GTPases.

Research Products

• [Journal Article] IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes. (2016)
  • Author(s): Man SM, Karki R, Sasai M, Place DE, Kesavardhana S, Temirov J, Frase S, Zhu Q, Malireddi RK, Kuriakose T, Peters JL, Neale G, Brown SA, Yamamoto M, Kanneganti TD.
  • Journal Title: Cell Volume: 167 Pages: 382-396
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen. (2015)
  • Author(s): Lee Y, Sasai M, Ma JS, Sakaguchi N, Ohshima J, Bando H, Saitoh T, Akira S, Yamamoto M
  • Journal Title: Cell Rep. Volume: 13 Pages: 223233-223233
  • DOI: 10.1016/j.celrep.2015.09.005
  • NAID: 120007001422
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Interferon-induced activation of cell-autonomous immunity against vacuolar pathogens (2016)
  • Author(s): Masahiro Yamamoto
  • Organizer: The 45th Annual meeting of the Japanese Society for Immunology
  • Place of Presentation: 沖縄
  • Year and Date: 2016-12-05
  • Int'l Joint Research / Invited
• [Presentation] Mechanism of IFN-γ-inducible cell-autonomous immunity to intracellular pathogens (2016)
  • Author(s): Masahiro Yamamoto
  • Organizer: The 15th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 兵庫
  • Year and Date: 2016-09-06
  • Int'l Joint Research / Invited