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Elucidation of interferon-dependent host defense system against legal infectious disease-causing microbes for domestic animals

Research Project

Project/Area Number 19H00970
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 42:Veterinary medical science, animal science, and related fields
Research InstitutionOsaka University

Principal Investigator

YAMAMOTO MASAHIRO  大阪大学, 微生物病研究所, 教授 (00444521)

Co-Investigator(Kenkyū-buntansha) 高島 康弘  岐阜大学, 応用生物科学部, 准教授 (20333552)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥44,590,000 (Direct Cost: ¥34,300,000、Indirect Cost: ¥10,290,000)
Fiscal Year 2022: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2021: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2020: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywordsインターフェロン / トキソプラズマ / 家畜病原体 / 病原性因子 / CRISPRスクリーン / ブタ / 宿主免疫系 / 細胞自律的免疫系 / IRGB6 / 寄生胞膜 / GBP
Outline of Research at the Start

家畜の監視伝染病を引き起こす病原体であるトキソプラズマやサルモネラに対するにインターフェロン依存的な生体防御応答を解析し、PVM1の解析によって病原体含有膜上の非自己性の本体を明らかにする。マウス・ヒト研究で得られた知見が豚で適用できるのかin vitro・in vivo試験し、我が国での豚のトキソプラズマ生ワクチン使用のための基礎データを蓄積する。

Outline of Final Research Achievements

Toxoplasma is one of the pathogenic organisms that cause notifiable diseases in livestock. Toxoplasma is an obligate intracellular parasitic protozoan capable of infecting the cells of all warm-blooded animals with nuclei. It is estimated that about one-third of the world's population is infected with Toxoplasma, though many infections are asymptomatic. However, in immunocompromised humans and animals, it can cause fatal toxoplasmosis. Additionally, Toxoplasma is among the top five pathogens causing foodborne illnesses in the United States, leading to economic losses and a decrease in quality of life. Therefore, understanding its parasitological characteristics from an agricultural perspective was necessary. This study identified new pathogenic molecules, particularly IWS1 and GRA72.

Academic Significance and Societal Importance of the Research Achievements

本研究はトキソプラズマの病原性における転写因子IWS1の重要性を明らかにし、新たな治療標的の可能性を示した。IWS1およびROP18の機能とその相互作用の理解が進むことで、トキソプラズマのヒトおよび家畜感染症に対する新しい治療法の開発に寄与することが期待される。またトキソプラズマ原虫は一度感染すると、完全に排除することは不可能で一生涯に渡って感染し続けるが、本研究で同定された多数の病原性因子はトキソプラズマ原虫の『弱点』であり、それらを標的とした様々な新規治療法や家畜動物用のワクチンの開発が大いに期待される。

Report

(6 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Comments on the Screening Results   Annual Research Report
  • Research Products

    (14 results)

All 2024 2023 2022 2021 2019

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Funded Workshop (1 results)

  • [Journal Article] Host genetics highlights IFN-γ-dependent Toxoplasma genes encoding secreted and non-secreted virulence factors in in?vivo CRISPR screens2023

    • Author(s)
      Tachibana Yuta、Hashizaki Emi、Sasai Miwa、Yamamoto Masahiro
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 6 Pages: 112592-112592

    • DOI

      10.1016/j.celrep.2023.112592

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A genetic method specifically delineates Th1-type Treg cells and their roles in tumor immunity2023

    • Author(s)
      Okamoto Masaaki、Sasai Miwa、Kuratani Ayumi、Okuzaki Daisuke、Arai Masaya、Wing James B.、Sakaguchi Shimon、Yamamoto Masahiro
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 7 Pages: 112813-112813

    • DOI

      10.1016/j.celrep.2023.112813

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Toxoplasma IWS1 Determines Fitness in Interferon-γ-Activated Host Cells and Mice by Indirectly Regulating ROP18 mRNA Expression.2023

    • Author(s)
      Hashizaki Emi、Sasai Miwa、Okuzaki Daisuke、Nishi Tsubasa、Kobayashi Takashi、Iwanaga Shiroh、Yamamoto Masahiro
    • Journal Title

      mBio

      Volume: 14 Issue: 1

    • DOI

      10.1128/mbio.03256-22

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Uncovering a novel role of PLCβ4 in selectively mediating TCR signaling in CD8+ but not CD4+ T cells2021

    • Author(s)
      Sasai Miwa、Ma Ji Su、Okamoto Masaaki、Nishino Kohei、Nagaoka Hikaru、Takashima Eizo、Pradipta Ariel、Lee Youngae、Kosako Hidetaka、Suh Pann-Ghill、Yamamoto Masahiro
    • Journal Title

      Journal of Experimental Medicine

      Volume: 218 Issue: 7

    • DOI

      10.1084/jem.20201763

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cell-autonomous <i>Toxoplasma</i> killing program requires Irgm2 but not its microbe vacuolar localization2021

    • Author(s)
      Pradipta Ariel、Sasai Miwa、Motani Kou、Ma Ji Su、Lee Youngae、Kosako Hidetaka、Yamamoto Masahiro
    • Journal Title

      Life Science Alliance

      Volume: 4 Issue: 7 Pages: e202000960-e202000960

    • DOI

      10.26508/lsa.202000960

    • NAID

      120007185166

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasmodium UIS3 avoids host cell-autonomous exclusion that requires GABARAPs but not LC3 and autophagy2021

    • Author(s)
      Pradipta Ariel、Bando Hironori、Ma Ji Su、Tanaka Shun、Sasai Miwa、Yamamoto Masahiro
    • Journal Title

      Parasitology International

      Volume: 83 Pages: 102335-102335

    • DOI

      10.1016/j.parint.2021.102335

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CXCR4 regulates Plasmodium development in mouse and human hepatocytes2019

    • Author(s)
      Bando Hironori、Pradipta Ariel、Iwanaga Shiroh、Okamoto Toru、Okuzaki Daisuke、Tanaka Shun、Vega-Rodr?guez Joel、Lee Youngae、Ma Ji Su、Sakaguchi Naoya、Soga Akira、Fukumoto Shinya、Sasai Miwa、Matsuura Yoshiharu、Yuda Masao、Jacobs-Lorena Marcelo、Yamamoto Masahiro
    • Journal Title

      Journal of Experimental Medicine

      Volume: 216 Issue: 8 Pages: 1733-1748

    • DOI

      10.1084/jem.20182227

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Toxoplasma Effector GRA15-Dependent Suppression of IFN-γ-Induced Antiparasitic Response in Human Neurons2019

    • Author(s)
      Bando Hironori、Lee Youngae、Sakaguchi Naoya、Pradipta Ariel、Sakamoto Ryoma、Tanaka Shun、Ma Ji Su、Sasai Miwa、Yamamoto Masahiro
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 9 Pages: 140-140

    • DOI

      10.3389/fcimb.2019.00140

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] The novel VeDTR mouse system reveals roles of immune cells in anti-tumor immunity2024

    • Author(s)
      Masahiro Yamaomto
    • Organizer
      The 2nd Doherty Institute & partners IFReC Immunology Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] トキソプラズマ原虫に対する宿主セルオートノマス免疫系とその破綻2023

    • Author(s)
      山本雅裕
    • Organizer
      第75回 日本細胞生物学会大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 病原性寄生虫トキソプラズマの感染免疫学2023

    • Author(s)
      山本雅裕
    • Organizer
      第23回 免疫サマースクール
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Identification of secreted and non-secreted Toxoplasma virulence factors by in vivo CRISPR screens2023

    • Author(s)
      Masahiro Yamamoto
    • Organizer
      The 32nd Hot Spring Harbor International Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Funded Workshop] The 20th Awaji International Forum on Infection and Immunity2022

    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2025-01-30  

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