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Role of p62-related autophagy adaptor proteins in anti-microbial host defense

Research Project

Project/Area Number 16K19153
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionOsaka University

Principal Investigator

Lee Youngae  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) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsオートファジー / アダプター / 獲得免疫 / トキソプラズマ / p62 / NDP52 / Nbr1 / IFN-gamma / Toxoplasma / Ubiquitin / 獲得免疫系
Outline of Final Research Achievements

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.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2018 2017

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

  • [Journal Article] Essential role for GABARAP autophagy proteins in interferon-inducible GTPase-mediated host defense2017

    • Author(s)
      Sasai Miwa、Sakaguchi Naoya、Ma Ji Su、Nakamura Shuhei、Kawabata Tsuyoshi、Bando Hironori、Lee Youngae、Saitoh Tatsuya、Akira Shizuo、Iwasaki Akiko、Standley Daron M、Yoshimori Tamotsu、Yamamoto Masahiro
    • Journal Title

      Nature Immunology

      Volume: 18 Issue: 8 Pages: 899-910

    • DOI

      10.1038/ni.3767

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] An effector IRG is a critical factor mediating interferon-γ-induced ubiquitin decoration of Toxoplasma gondii parasitophorous vacuoles2018

    • Author(s)
      Youngae Lee
    • Organizer
      Forum Cheju 19
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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