Elucidation of host recognition and immune control mechanisms for pathogenic lipids in acid-fast bacteria.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07550
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Kagoshima University
• Principal Investigator: Hara Hiromitsu 鹿児島大学, 医歯学域医学系, 教授 (20392079)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 抗酸菌 / 自然免疫 / マクロファージ / 結核 / ハンセン病

Outline of Final Research Achievements

We identified host innate immune receptors that recognizes mycolic acid and phenolic glycolipid, which are cell wall lipids of acid-fast bacteria, and attempted to elucidate its role in the pathogenesis. The mycolic acid receptor TREM2 was suggested to be involved in the immune evasion of mycobacteria by inducing permissive activation of macrophages and suppressing the bactericidal Mφ activation mediated by Mincle. PGLR, identified as a PGL receptor, was found to be essential for the production of MCP-1 induced by PGL in macrophages, and was suggested to be involved in the immune evasion of Mycobacterium tuberculosis mediated by MCP-1. To clarify the role of PGLR in the demyelination mechanism induced by PGL-1 expressed by Mycobacterium leprae, we established a mouse sciatic nerve infection model of leprosy.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

我々の研究によって、結核菌やらい菌などの病原性抗酸菌が発現する病原性脂質が、宿主が発現する自然免疫受容体に作用することでその病原性を発揮することが明らかになりつつある。この分子機構が明らかになれば、結核やハンセン病の新しい治療薬の開発に資するものと考えられる。