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Leishmania parasites as biological resources for immunomodulatory molecules

Research Project

Project/Area Number 20K21516
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Goto Yasuyuki  東京大学, 大学院農学生命科学研究科(農学部), 准教授 (50553434)

Co-Investigator(Kenkyū-buntansha) 中尾 洋一  早稲田大学, 理工学術院, 教授 (60282696)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsリーシュマニア / 生物資源 / 免疫制御
Outline of Research at the Start

慢性的な感染を特徴とする寄生虫は、宿主適応を生存の必須条件とする。一方、我々の生体防御機構も寄生虫感染という選択圧によって形成されてきた。我々と寄生虫は共進化を遂げたパートナーであり、寄生虫が宿主から一方的に恩恵を受けるのではなく、宿主も寄生虫から恩恵を受けることができると考えられる。代表的な例として、寄生虫が免疫を制御する分子機構を明らかにすれば、がんやアレルギーといった免疫関連疾患を制御する薬剤の開発に応用可能である。本研究ではマクロファージ(Mφ)寄生性原虫であるリーシュマニア原虫がもつMφの殺原虫能の抑制能力や液性免疫誘導能力に焦点を当て、免疫制御を担う原虫因子の同定をめざす。

Outline of Final Research Achievements

Leishmania parasites proliferate within macrophages (Mφ) in the mammalian host, and they need to manipulate Mφ to ensure its efficient survival. In this study, we focused on the ability of Leishmania to regulate Mφ and aimed to identify the protozoan factors responsible for this regulation. We conducted our research by establishing screening methods, fractionating protozoan extracts, and identifying active substances. In FY2020 we succeeded to establish various screening assays, and in FY2021 fractionation-based search of active compounds were performed using the mentioned assay systems. As a result of screening, several candidate molecules were identified, but when recombinant forms of them were produced, they did not show desired activities. Therefore, we decided to improve the assays for further screening. Some active fractions were determined by the new assay, whereas we could not reach to identification of active molecules.

Academic Significance and Societal Importance of the Research Achievements

寄生虫は宿主体内での生存のために宿主免疫応答を制御することが知られている。その分子機構を明らかにすれば、寄生虫疾患の対策はもちろんのこと、それ以外の疾患、つまりがんやアレルギーなど免疫関連疾患を制御可能な薬剤の開発に貢献することも期待できる。本研究を通して、リーシュマニア原虫には宿主免疫応答を修飾する物質が複数あること、そしてそれらはスクリーニングで同定可能であることを示した点で、将来への発展性も期待できる成果と言える。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2022 2021

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Autochthonous <i>Leishmania infantum</i> in Dogs, Zambia, 20212022

    • Author(s)
      Squarre D, Chambaro HM, Hayashida K, Moonga LC, Qiu Y, Goto Y, Oparaocha E, Mumba C, Muleya W, Bwalya P, Chizimu J, Chembensofu M, Simulundu E, Mwasinga W, Banda N, Mwenda R, Yamagishi J, Nalubamba KS, Banda F, Munyeme M, Sawa H, Fandamu P
    • Journal Title

      Emerging Infectious Diseases

      Volume: 28 Issue: 4 Pages: 888-890

    • DOI

      10.3201/eid2804.212378

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Parasitomimetics: Can We Utilize Parasite-Derived Immunomodulatory Molecules for Interventions to Immunological Disorders?2022

    • Author(s)
      Nagai Kazuki、Goto Yasuyuki
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 824695-824695

    • DOI

      10.3389/fimmu.2022.824695

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatomegaly Associated with Non-Obstructive Sinusoidal Dilation in Experimental Visceral Leishmaniasis2021

    • Author(s)
      Maeda Kota、Sadoughi Sonya、Morimoto Ayako、Uchida Kazuyuki、Chambers James K.、Sanjoba Chizu、Yamagishi Junya、Goto Yasuyuki
    • Journal Title

      Pathogens

      Volume: 10 Issue: 11 Pages: 1356-1356

    • DOI

      10.3390/pathogens10111356

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current Approaches to the Development of a Vaccine against CL2021

    • Author(s)
      Goto Yasuyuki
    • Journal Title

      Clinical Evaluation

      Volume: 49 Pages: 225-232

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Editorial: Emerging Concepts of Innate Immune Responses to Neglected Tropical Diseases2021

    • Author(s)
      Duthie Malcolm S.、Goto Yasuyuki
    • Journal Title

      Frontiers in Immunology

      Volume: 12 Pages: 658553-658553

    • DOI

      10.3389/fimmu.2021.658553

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Hemophagocytosis induced by Leishmania donovani infection is beneficial to parasite survival within macrophages2021

    • Author(s)
      Yasuyuki Goto
    • Organizer
      The 19th Awaji International Forum on Infection and Immunity
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 内臓型リーシュマニア症の免疫病態:原虫感染による血球貪食の誘導とその意義2021

    • Author(s)
      後藤康之
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Current approaches to the development of a vaccine against CL2021

    • Author(s)
      Yasuyuki Goto
    • Organizer
      Cutaneous leishmaniasis webinar: Knowledge gaps and challenges in managing patients suffering from CL
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2020-08-03   Modified: 2023-12-25  

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