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Development of novel antiacid bacterial immunotherapy based on mucosal immune response

Research Project

Project/Area Number 19K22645
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research InstitutionNational Institutes of Biomedical Innovation, Health and Nutrition

Principal Investigator

IIJIMA NORIFUMI  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 細胞核輸送ダイナミクスプロジェクト, サブプロジェクトリーダー (40612552)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords粘膜免疫増強 / 粘膜免疫 / 末梢組織免疫増強 / 組織局在型メモリー T 細胞
Outline of Research at the Start

結核菌感染は肺組織に潜伏感染を起こすことによって長期間生存することになる。最も致命的なのは、結核菌が再活性化した患者に適切な治療を施さない場合である。抗結核薬は、長期間投与することにより結核菌を駆逐することが可能であるが、多剤耐性結核菌などに対しては、効果を発揮しない例が増加している。そこで、申請者が先の研究で発見した、長期間粘膜組織で病原体防御能を維持できるメモリーリンパ球クラスターを応用して、これまでにない新しい抗酸菌治療法の基盤となる研究計画を提案する。

Outline of Final Research Achievements

Anti-acid bacilli such as Mycobacterium tuberculosis and Leprosy are capable of parasitizing and reproducing in macrophages, the cells responsible for immunity, and are therefore highly virulent and can survive in the body for a long time. Therefore, if they cannot be treated with existing antibacterial drugs, the growth of anti-acid bacilli can become uncontrollable, resulting in life-threatening consequences. Therefore, we propose a research plan that will serve as the basis for a new immunotherapy against multidrug-resistant acid-fast bacteria, focusing on the reinforcement of immune defense in mucosal tissues instead of conventional chemotherapies. The goal of this project is to provide the basis for a new therapeutic platform against multidrug-resistant acid-fast bacteria in preparation for a pandemic.

Academic Significance and Societal Importance of the Research Achievements

抗酸菌の一つである結核菌は世界10大死因の一つに数えられ、2016年には世界中で1,040万人が結核に罹患し、170万人が結核で死亡している。抗結核薬を長期間投与することにより、結核菌を駆逐することが可能であるが、多剤耐性結核菌(MDR) や広範囲薬剤耐性結核菌(XDR)に対しては、効果を発揮しない例が増加している。最も致命的なのは、すべての抗結核薬に耐性の結核菌の将来的な蔓延である。
本研究では、耐性菌を生み出す化学療法ではなく、粘膜組織の免疫増強効果を目的とした免疫療法のプラットフォームの構築を検討することで、今後の多剤耐性菌にも対処できる治療方法の新しい方向性を示すことに成功した。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2021 2020 2019

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism2021

    • Author(s)
      LeeML, Matsunaga H, Sugiura Y, Hayasaka T, Yamamoto I, Imoto D, SuematsuM, Iijima N, Kimura K, Diano S, Toda C.
    • Journal Title

      Nature Communications

      Volume: Not determined Issue: 1 Pages: 2330-2330

    • DOI

      10.1038/s41467-021-22431-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Activation of prodynorphin neurons in the dorsomedial hypothalamus inhibits food intake and promotes positive valence2020

    • Author(s)
      Imoto D, Yamamoto I, Matsunaga H, Yonekura T, Lee ML, Kato KX, Yamasaki T, Otsuguro K, Horiuchi M, Iijima N, Kimura K, Toda C.
    • Journal Title

      bioRxiv

      Volume: 0 Pages: 1-17

    • DOI

      10.1101/2020.07.02.183780

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism2020

    • Author(s)
      LeeML, Matsunaga H, Sugiura Y, Hayasaka T, Yamamoto I, Imoto D, SuematsuM, Iijima N, Kimura K, Diano S, Toda C.
    • Journal Title

      bioRxiv

      Volume: 0 Pages: 1-40

    • DOI

      10.1101/2020.05.18.056374

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] Memory Lymphocyte Clusters in Genital Immunity: Role of Tissue-Resident Memory T Cells (TRM).2020

    • Author(s)
      Iijima N
    • Journal Title

      Current Topics in Microbiology and Immunology

      Volume: 426 Pages: 83-117

    • DOI

      10.1007/82_2020_213

    • ISBN
      9783030517465, 9783030517472
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection.2019

    • Author(s)
      Amezcua Vesely MC, Pallis P, Bielecki P, Low JS, Zhao J, Harman CCD, Kroehling L, Jackson R, Bailis W, Licona-Limon P, Xu H, Iijima N, Pillai PS, Kaplan DH, Weaver CT, Kluger Y, Kowalczyk MS, Iwasaki A, Pereira JP, Esplugues E, Gagliani N, Flavell RA.
    • Journal Title

      Cell

      Volume: 178 Issue: 5 Pages: 1176-1188

    • DOI

      10.1016/j.cell.2019.07.032

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Migrant memory B cells secrete luminal antibody in the vagina.2019

    • Author(s)
      2)Oh JE*, Iijima N*, Song E, Lu P, Klein J, Jiang R, Kleinstein SH, Iwasaki A (* equally contributed).
    • Journal Title

      Nature

      Volume: 571 Issue: 7763 Pages: 122-126

    • DOI

      10.1038/s41586-019-1285-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid quantification of NETs in vitro and in whole blood samples by imaging flow cytometry2019

    • Author(s)
      Lelliott PM, Momota M, Lee MSJ, Kuroda E, Iijima N, Ishii KJ, Coban C.
    • Journal Title

      Cytometry A

      Volume: .. Issue: 5 Pages: 565-578

    • DOI

      10.1002/cyto.a.23767

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 粘膜ウィルス感染に対する末梢組織生体防御機構の解明に取り組んで2019

    • Author(s)
      10)飯島則文
    • Journal Title

      The Japanese Journal of Antibiotics

      Volume: 72 Pages: 25-30

    • NAID

      40021853607

    • Related Report
      2019 Research-status Report
  • [Presentation] 生殖器粘膜ウィルス感染に対する末梢組織免疫制御機構の解明2019

    • Author(s)
      飯島則文
    • Organizer
      第 92 回 日本細菌学会総会 シンポジウム3 生体フロントラインバリアの破綻と感染症
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Migrant memory B cells secrete luminal antibody in the vagina2019

    • Author(s)
      Norifumi Iijima
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 組織局在型メモリー T 細胞に着目した潜伏感染ウィルスの再活性化機構の解明2019

    • Author(s)
      飯島則文
    • Organizer
      -PRIDE 研究成果発表会 重症・難治性感染症の理解と予防・治療法の開発に向けて~若手研究者たちの挑戦~
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Peripheral immune control of latent virus infection2019

    • Author(s)
      Norifumi Iijima
    • Organizer
      大阪大学免疫学フロンティア研究センター IFReC セミナー
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-07-04   Modified: 2022-01-27  

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