• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of neutrophil differentiation suppression mechanism by Clostridium perfringens alpha-toxin

Research Project

Project/Area Number 18K07129
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionTokushima Bunri University

Principal Investigator

Takehara Masaya  徳島文理大学, 薬学部, 講師 (40742705)

Co-Investigator(Kenkyū-buntansha) 永浜 政博  徳島文理大学, 薬学部, 教授 (40164462)
小林 敬子  徳島文理大学, 薬学部, 助教 (90170315)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsウエルシュ菌 / 毒素 / 宿主免疫 / 好中球 / 細胞免疫 / 細菌毒素 / ガス壊疽 / 自然免疫 / Toll様受容体 / 細菌感染
Outline of Final Research Achievements

Clostridium perfringens produces α-toxin, suppresses neutrophil differentiation and impairs host immunity, but the mechanism is still unknown. In this study, we found that α-toxin does not affect the production of granulocyte colony-stimulating factor (G-CSF), which is involved in neutrophil differentiation, reduces G-CSF receptor expression in neutrophils, leading to inhibition of CSF-mediated cell differentiation signals. In addition, it was found that the decrease in G-CSF receptor expression was caused by the increase in ceramide production caused by α-toxin. Furthermore, it was found that α-toxin excessively activates the host immune responses and widely damages the host cells and organs. Thus, α-toxin is thought to disrupt host immunity by various mechanisms and contribute to the spread of Clostridium perfringens infection.

Academic Significance and Societal Importance of the Research Achievements

本研究で示した毒素の好中球分化に対する影響に着目した研究は世界的にも前例がほとんど無く、学術的にも極めて独創性が高いと考えられる。また、本研究で実施した研究手法は、さまざまな病原細菌の研究に応用可能で、発症や進行の機構が不明な細菌感染症の進行メカニズムの解明に寄与する可能性がある。このように、本研究の成果は、細菌感染症に対する新規な研究領域を開拓し、発症機序解明や治療に大きく貢献するものと期待する。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (9 results) (of which Invited: 2 results)

  • [Journal Article] Clostridium perfringens alpha-toxin inhibits myogenic differentiation of C2C12 myoblasts.2020

    • Author(s)
      Takehara M, Kobayashi K, Nagahama M
    • Journal Title

      Anaerobe

      Volume: 65 Pages: 102265-102265

    • DOI

      10.1016/j.anaerobe.2020.102265

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clostridium perfringens alpha-toxin specifically induces endothelial cell death by promoting ceramide-mediated apoptosis.2020

    • Author(s)
      Takehara M, Bandou H, Kobayashi K, Nagahama M
    • Journal Title

      Anaerobe

      Volume: 65 Pages: 102262-102262

    • DOI

      10.1016/j.anaerobe.2020.102262

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Granulocyte Colony-Stimulating Factor Does Not Influence Clostridium Perfringens α-Toxin-Induced Myonecrosis in Mice2019

    • Author(s)
      Takehara Masaya、Sonobe Yuuta、Bandou Hiroto、Kobayashi Keiko、Nagahama Masahiro
    • Journal Title

      Toxins

      Volume: 11 Issue: 9 Pages: 509-509

    • DOI

      10.3390/toxins11090509

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clostridium perfringens α-toxin impairs granulocyte colony-stimulating factor receptor-mediated granulocyte production while triggering septic shock2019

    • Author(s)
      Takehara Masaya、Seike Soshi、Sonobe Yuuta、Bandou Hiroto、Yokoyama Saki、Takagishi Teruhisa、Miyamoto Kazuaki、Kobayashi Keiko、Nagahama Masahiro
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 45-45

    • DOI

      10.1038/s42003-019-0280-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Host Defense against Bacterial Infection and Bacterial Toxin-induced Impairment of Innate Immunity2018

    • Author(s)
      Takehara Masaya
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 138 Issue: 10 Pages: 1249-1253

    • DOI

      10.1248/yakushi.18-00102

    • NAID

      130007493874

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2018-10-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ウエルシュ菌と宿主の相互作用に関する研究2021

    • Author(s)
      竹原正也
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] A型ウエルシュ菌の病原性発現機構に関する研究2020

    • Author(s)
      竹原正也、小林敬子、永浜政博
    • Organizer
      第73回日本細菌学会中国・四国支部総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ウエルシュ菌α毒素による宿主免疫撹乱の分子機構2020

    • Author(s)
      竹原正也、小林敬子、永浜政博
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] ウエルシュ菌α毒素による宿主免疫応答の活性化2019

    • Author(s)
      竹原正也、小林敬子、永浜政博
    • Organizer
      第66回トキシンシンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] ウエルシュ菌α毒素による宿主免疫応答の撹乱2019

    • Author(s)
      竹原正也、小林敬子、永浜政博
    • Organizer
      第31回微生物シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] ウエルシュ菌α毒素による血管内皮細胞の障害2019

    • Author(s)
      竹原正也、小林敬子、永浜政博
    • Organizer
      第72回日本細菌学会中国・四国支部総会
    • Related Report
      2019 Research-status Report
  • [Presentation] ウエルシュ菌α毒素によるToll様受容体を介した宿主免疫の撹乱2019

    • Author(s)
      竹原正也、小林敬子、永浜政博
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ウエルシュ菌α毒素による好中球の産生抑制機構の解明2018

    • Author(s)
      竹原正也, 小林敬子, 永浜政博
    • Organizer
      第65回トキシンシンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Toll様受容体を介した宿主の免疫反応に対するウエルシュ菌α毒素の影響2018

    • Author(s)
      竹原正也、小林敬子、永浜政博
    • Organizer
      第71回日本細菌学会中国・四国支部総会
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi