Analysis of immunological mechanisms for persistent infection with Cryptococcus neoformans and its reactivation using a novel animal model

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02965
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Tohoku University
• Principal Investigator: Kawakami Kazuyoshi 東北大学, 医学系研究科, 名誉教授 (10253973)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: クリプトコックス / 潜在性感染 / 内因性再燃 / 動物モデル / 免疫機序

Outline of Final Research Achievements

Recently, it has been considered that cryptococcosis may be developed by reactivation of latently infected Cryptococcus neoformans in lungs. In our previous study, we succeeded in creating a latent infection (LCNI) model using a transgenic mouse that highly expresses a cryptococcal-specific T cell antigen receptor. In the present study, we attempted to create an endogenous reactivation model by administering various immunosuppressants to this LCNI model. When fingolimod, a novel immunosuppressant, was administered to this model, an increase in the number of fungi in the lungs and a decrease in Th1 immune responses were observed. Using this model, we focused our analysis on effector T cells and memory T cells in the lungs to clarify the immune mechanisms leading from LCNI to endogenous reactivation.

Free Research Field

感染症学

Academic Significance and Societal Importance of the Research Achievements

近年、クリプトコックス症は潜在性感染後に免疫不全により内因性再燃すると考えられている。本研究では、我々が樹立した本真菌に特異的なT細胞受容体を高発現するトランスジェニックマウスを用いることで作製した潜在性感染モデルに免疫抑制剤を投与することで内因性再燃モデルの作製に成功した。今後、より詳細な免疫機序を明らかにすることで、臨床的に重要なクリプトコックス髄膜炎の発症病態の解明に迫ることができるものと期待される。