Host defense mechanisms against Aspergillus fumigatus

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07063
• 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: Chiba University
• Principal Investigator: Saijo Shinobu 千葉大学, 真菌医学研究センター, 准教授 (60396877)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: サイトカイン / 感染免疫 / 真菌感染 / 感染防御機構

Outline of Final Research Achievements

Aspergillus fumigatus is a ubiquitous, yet potentially pathogenic, mold. The immune system employs innate receptors, such as dectin-1, to recognize fungal pathogens, but the immunological networks that afford protection are poorly explored. Here, we investigated the role of dectin-1 in anti-A. fumigatus response in an experimental model of acute invasive aspergillosis. Mice lacking dectin-1 presented enhanced signs of inflammation, with increased production of inflammatory cytokines and neutrophil infiltration, quickly succumbing to the infection. The main effector function of dectin-1 was the preservation of the NK cell population in the kidneys by the provision of the cytokine IL-15. While the depletion of NK cells impaired host defense in wild-type mice, IL-15 administration restored antifungal responses in dectin-1 deficient mice.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

Dectin-1は、糖鎖を認識する分子群であるC型レクチンファミリーに属する分子である。本研究では、このDectin-1が病原性真菌A. fumigatus の感染防御に非常に重要な役割を果たしていることを見出した。そのメカニズムとして、Dectin-1からのシグナルがIL-15の産生を誘導しNK細胞を介して菌体を排除していることを明らかにした。この結果は、大きな社会問題となっている真菌感染症に対する新たな治療戦略へつながる可能性がある。