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

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Tokushima 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
• Keywords: ウエルシュ菌 / 毒素 / 宿主免疫 / 好中球 / 細胞免疫

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.

Free Research Field

細菌学

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。