Pathogenesis of allergic inflammation induced by fungal cell wall chitin

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07476
• 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: National Institute of Infectious Diseases (2021-2023); Chiba University (2020)
• Principal Investigator: Yasunori Muraosa 国立感染症研究所, 安全実験管理部, 主任研究官 (10574668)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: キチン / Dectin-2 / C型レクチン / IL-1α / O-結合型糖鎖 / アレルギー性炎症 / Aspergillus fumigatus / 真菌

Outline of Final Research Achievements

Although the mechanism of chitin-induced allergic reactions is gradually being elucidated, the full extent of the mechanism remains to be elucidated. In this study, we aimed to elucidate the recognition mechanism of fungal cell wall chitin by the organism and the mechanism by which it induces allergic reactions.
In this study, we found that the O-linked glycan of LdpA expressed in yeast Pichia pastoris are recognized by Dectin-2. Chitin particles were recognized intracellularly after phagocytosis by BMDCs and induced IL-1α production and cell death, but the mechanism was not elucidated. LdpA and chitin induce Th2-type airway inflammation in a synergistic and Dectin-2-dependent manner.

Free Research Field

真菌感染症

Academic Significance and Societal Importance of the Research Achievements

世界保健機関（WHO）によると、喘息は子供の間で最も一般的な慢性疾患であり、世界中で2億6,200万人以上が罹患している。喘息の根本的な原因は未だ明らかにされていないが、その危険因子の1つが真菌胞子の吸入であるとされている。我々が本研究でキチン粒子とキチン結合性糖タンパク質のO-結合型糖鎖が相乗的かつDectin-2依存的にTh2型気道炎症を誘導することを明らかにしたことにより、喘息などのアレルギー性疾患の発症機序の解明に寄与できたと考えている。