Lung resident memory Th2 cells amealiorates pulmonary cryptococcosis caused by Cryptococcus gattii

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07507
• 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
• Principal Investigator: Ueno Keigo 国立感染症研究所, 真菌部, 主任研究官 (10550220)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 肺常在性記憶T細胞 / クリプトコックス症 / 肉芽腫 / 多核巨細胞 / Th2

Outline of Final Research Achievements

The pathogenic fungus Cryptococcus gattii causes pulmonary cryptococcosis. In this study, we developed an intranasal vaccine against this infection. This vaccine induced lung resident memory Th2 cells =lung TRM2 and ameliorated the disease with granuloma formation. In IL-4/IL-13 double-deficient (DKO) mice, the granuloma formation and the protective effect was downregulated. The immunosuppressive agent FTY720 had no effect on this protection. Adoptive transfer of lung TRM2 rendered Rag1-deficient mice resistant to the infection. Coculture of lung TRM2 and macrophages in the presence of the antigen formed multinucleated giant cells (MGCs), while lung TRM2 from DKO mice did not induce MGCs. These MGCs phagocytosed live C. gattii cells independently of opsonization. Taken together, we concluded that the vaccine-related lung TRM2 induces granulomas via IL-4/IL-13 and suppresses C. gattii infection.

Free Research Field

医真菌学, 免疫学

Academic Significance and Societal Importance of the Research Achievements

この研究は, 肺常在記憶Th2細胞 = lung TRM2の肺クリプトコックス症に対する防衛的役割を明らかにした. lung TRM2は好酸球を誘導するものの, 好酸球だけでは十分な感染防御効果は得られず, II型肉芽腫を誘導することでクリプトコックス症を制御した. Lung TRM2はマクロファージとの共培養で多核巨細胞を誘導した. これらの新しい知見は, クリプトコックス症ワクチンの開発において有益である.