Role of microbiome on neutrophil recruitment in tissue injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03716
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Honda Masaki 熊本大学, 大学院生命科学研究部(医), 特定研究員 (80573609)
• Co-Investigator(Kenkyū-buntansha): 日比 泰造 熊本大学, 大学院生命科学研究部(医), 教授 (10338072)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 好中球 / 腸内細菌叢 / 組織修復 / 生体イメージング

Outline of Final Research Achievements

1. Tissue repair of the liver in Abx-treated mice: Using two-photon laser-scanning microscopy (TPLSM) and liver thermal injury methods, we found that 1) neutrophils phagocytosed the necrotic cells and contributed to the removal, and 2) the removal of necrotic cells, vascular regeneration and collagen deposition was delayed in Abx-treated mice.
2. Changes in neutrophil dynamics during liver injury: Using flow cytometry, we found that administration of Abx reduced the total number of neutrophils in blood and bone marrow (BM). A more detailed examination revealed that both Ly6Gint and Ly6Ghi neutrophils was affected. When the liver was thermally injured and observed with a TPLSM for 4 hours, neutrophil accumulation at the damaged site was suppressed. These results suggest that use of broad-spectrum Abx not only reduces the number of neutrophils in blood and BM, but also impairs neutrophil accumulation at the site of liver damage, delaying the tissue repair.

Free Research Field

小児外科学

Academic Significance and Societal Importance of the Research Achievements

組織修復過程における免疫機構を解明することは全ての外科手術において重大な課題である。近年、免疫システムの構築において腸内細菌叢が重要な役割を果たすことが明らかになってきているが、そのメカニズムについては不明な点が多い。本研究では、広域抗生剤投与により血中・骨髄中の好中球数減少がもたらされることに加え、肝臓障害部位への好中球集積が障害され組織修復過程が遅延することを示した。これらは組織修復メカニズムの解明において、腸内細菌叢-好中球-組織修復の相互作用に着目した新たな知見であると考える。