Flagella and TLR5-mediated symbiosis and co-evolution between gut commensal bacteria and host

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20576
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0601:Agricultural chemistry and related fields
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Suzuki Shunya 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究員 (50964227)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 腸内細菌 / べん毛 / 免疫 / 共生 / フラジェリン

Outline of Final Research Achievements

Immune responses to flagellin, the major subunit protein of the bacterial flagellum, are critical for the recognition and elimination of flagellated pathogens. Although commensal bacteria also produce flagellins, the mechanisms by which flagellated commensal bacteria are able to colonize the gut and evade immune clearance remain unknown. This study aimed to investigate the immunological properties of flagellated commensal bacteria prevalent in the human gut, both in vitro and in vivo. In vitro analysis revealed that some flagellins exhibited attenuated immunological activity, while others demonstrated robust immunological activity. This difference was not observed in gnotobiotic mice with each flagellated commensal, despite comparable gut colonization between the commensals. The commensals elicited only modest immune responses in the gut. These findings indicate that commensal bacteria with significant immunostimulatory potential also colonize the gut and evade the immune system.

Free Research Field

応用微生物学

Academic Significance and Societal Importance of the Research Achievements

我々の免疫系は、病原細菌と共生細菌に対して「排除」と「許容」という相反する応答を示し、生体の恒常性を維持している。これまでに、免疫系が病原細菌を排除するメカニズムはよく研究されてきた。一方で、腸内共生細菌がなぜ免疫系によって排除されずに、腸内に常在できるのかは未解明な点が多い。本研究成果は、腸内共生細菌が腸内に常在できる仕組みの一端を明らかにしたものであり、腸内細菌叢の形成原理のみならず、生体の恒常性維持機構の包括的な理解にも繋がる、学術的・社会的意義のある研究成果である。