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Elucidation of mucosal immunity induction mechanism by microbial adhesion signal and application to mucosal adjuvant development

Research Project

Project/Area Number 16K08241
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionGihu University of Medical Science (2018-2019)
Gifu Pharmaceutical University (2016-2017)

Principal Investigator

Sugiyama Tsuyoshi  岐阜医療科学大学, 薬学部, 教授 (70268001)

Co-Investigator(Kenkyū-buntansha) 上田 浩  岐阜大学, 工学部, 教授 (50253779)
高橋 圭太  岐阜薬科大学, 薬学部, 助教 (50634929)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords腸管出血性大腸菌 / シトロバクター・ローデンティウム / III型分泌機構 / アクチン重合 / RhoGEF / Rho GTPase / 免疫学
Outline of Final Research Achievements

Enterohemorrhagic Escherichia coli and Citrobacter rodentium inject proteins derived from the bacterium into the infected host by a mechanism called type III secretion system, then, exert various effects on the host cell. These bacteria bind Tir, which is an effector of the type III secretion system, as a receptor for adhesion, and firmly adhere to host cells with induction of actin polymerization. The effect of intracellular actin polymerization during this adhesion was examined both in vitro and in vivo. The in vitro results suggest that the differential expression of various genes depending on the presence or absence of actin polymerization, and the in vivo results suggest that actin polymerization influences mucosal immunity induction.

Academic Significance and Societal Importance of the Research Achievements

粘膜は様々な感染症の病原体の侵入門戸となるため、粘膜免疫が誘導されることは病原体の侵入を阻止する感染防御に最も有効な免疫を付与するものと考えられる。本研究では粘膜免疫を誘導する細菌が細胞に接着し、アクチン重合を誘導することに着目し、アクチン重合が粘膜上皮細胞の遺伝子発現に変化を与え、粘膜免疫誘導になんらかの影響を及ぼすことを示唆する結果を得た。このアクチン重合の働きをさらに解明し応用することによって、感染防御に有効な粘膜免疫を誘導するワクチンの開発が期待できる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017 2016

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

  • [Journal Article] The interaction between PLEKHG2 and ABL1 suppresses cell growth via the NF-κB signaling pathway in HEK293 cells2019

    • Author(s)
      Nishikawa Masashi、Nakano Shun、Nakao Hiromu、Sato Katsuya、Sugiyama Tsuyoshi、Akao Yukihiro、Nagaoka Hitoshi、Yamakawa Hisashi、Nagase Takahiro、Ueda Hiroshi
    • Journal Title

      Cellular Signalling

      Volume: 61 Pages: 93-107

    • DOI

      10.1016/j.cellsig.2019.04.016

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peyer’s Patches as a Portal for DNA Delivery by <i>Lactococcus lactis</i> <i>in Vivo</i>2018

    • Author(s)
      Ayumu Yano, Keita Takahashi, Yusuke Mori, Shiori Watanabe, Yuki Hanamura, Tsuyoshi Sugiyama, Naoki Inoue
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 2 Pages: 190-197

    • DOI

      10.1248/bpb.b17-00657

    • NAID

      130006329249

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 上皮細胞でのⅢ型分泌装置を介したアクチン重合はCitrobacter rodentium特異的分泌型IgA産生誘導に必須ではない2019

    • Author(s)
      鶴見駿、髙橋圭太、井上直樹、杉山剛志
    • Organizer
      第31回 微生物シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] KIAA0599 augments TRIF- and Myd88-dependent TLR signaling2018

    • Author(s)
      Tsuyoshi Sugiyama, Kanna Nakao, Ryo Hayami, Takuya Hasegawa, Keita Takahashi, Naoki Inoue, Takahiro Nagase, Hiroshi Ueda
    • Organizer
      Joint Meeting of the Society for Leukocyte Biology & the International Endotoxin and Innate Immunity Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 糞便移植を用いたデキストラン硫酸ナトリウム誘発マウス潰瘍性大腸炎モデルにおける腸内細菌叢と病態の関係の解析2017

    • Author(s)
      惠西丈彦、西科冴香、安田祐里花、村岡夏実、加藤大樹、 前川洋一、井上直樹、杉山剛志
    • Organizer
      第54 回日本細菌学会中部支部総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Rhoグアニンヌクレオチド交換因子PLEKHG3によるTRIF依存的シグナル増強作用2017

    • Author(s)
      中尾莞奈、早水良、秋元奈央、長谷川拓也、高橋圭太、 井上直樹、長瀬隆弘、上田浩、杉山剛志
    • Organizer
      第54 回日本細菌学会中部支部総会
    • Related Report
      2017 Research-status Report
  • [Presentation] A/E病変に伴うアクチンの重合が制御する宿主遺伝子発現2017

    • Author(s)
      安田祐里花、鶴見駿、早水良、惠西丈彦、高橋圭太、井上直樹、 杉山剛志
    • Organizer
      第21 回腸管出血性大腸菌感染症研究会参加
    • Related Report
      2017 Research-status Report
  • [Presentation] Rhoグアニンヌクレオチド交換因子KIAA0362のToll様受容体シグナルへの影響2017

    • Author(s)
      早水良、杉山剛志
    • Organizer
      第23回日本エンドトキシン・自然免疫研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 腸管上皮細胞におけるRho GTPase活性化のToll様受容体シグナルへの影響2016

    • Author(s)
      矢端文彦、中尾莞奈、早水良、田中秀幸、児玉雄大、高橋圭太、井上直樹、 長瀬隆弘、上田浩、杉山剛志
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2016
    • Place of Presentation
      岐阜
    • Year and Date
      2016-10-30
    • Related Report
      2016 Research-status Report
  • [Presentation] ARHGEF15 augments TRIF-dependent pathway of TLR signaling via enhancing the phosphorylation of IRF-32016

    • Author(s)
      Sugiyama T, Hasegawa T, Takahashi K, Inoue N., Nagase T., Ueda H.
    • Organizer
      14th Biennial Meeting of International Endotoxin and Innate Immunity Society
    • Place of Presentation
      ドイツ・ハンブルグ
    • Year and Date
      2016-09-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] エンドトキシン・自然免疫研究 21 エンドトキシン・自然免疫研究のフロンティアをめざして2018

    • Author(s)
      早水良、杉山剛志
    • Total Pages
      88
    • Publisher
      医学図書出版株式会社
    • Related Report
      2018 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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