Efferocytosis mediates Salmonella endurance during neutrophil-killing activities.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07027
• 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: Nagasaki University
• Principal Investigator: Hiyoshi Hirotaka 長崎大学, 熱帯医学研究所, 准教授 (00585599)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: サルモネラ / 好中球 / エフェロサイトーシス / 侵襲感染 / T3SS

Outline of Final Research Achievements

Salmonella can cause severe invasive infections under certain conditions. It has been shown that a virulence factor called type III secretion apparatus (T3SS-2) allows “Salmonella-containing vacuoles (SCVs)” to form and multiply within macrophages. However, their spread throughout the body remains unclear. In this study, we found that Salmonella can induce "efferocytosis" in which neutrophils take up the bacteria with each dead macrophage, through perforation of SCV using T3SS-2. Furthermore, they showed that this mechanism neutralizes the reactive oxygen species produced by neutrophils and enhances the viability of Salmonella within neutrophils, which in turn exacerbates invasive infections. The results were presented at conferences and published in an international journal (Cell Host Microbe 2022).

Free Research Field

細菌感染症学

Academic Significance and Societal Importance of the Research Achievements

宿主の恒常性に関わるエフェロサイトーシスを悪用した、サルモネラの好中球内における生存戦略は、本菌のみならず他の細胞内寄生菌においても共通な侵襲感染発症機構である可能性を見出している。また感染症関連の国際誌の中でもインパクトの高いCell Host and Microbe誌に掲載されたことからも本研究の成果における学術的な意義は高いと考える。現在、薬剤耐性のサルモネラが、アフリカや東・東南アジア諸国で問題となっているが、我々の研究により明らかにされたサルモネラ感染メカニズムを基盤とした、抗生物質だけに頼らない新規治療薬の開発につながることが今後期待される。