Verification of hypothesis for reactivation-induced cryptococcosis and clarification of its immunological mechanism using an animal model

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02851
• 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, 教授 (10253973)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: クリプトコックス / 潜伏感染 / メモリーT細胞 / 内因性再燃 / 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 the present study, we succeeded in establishing a mouse model of latent pulmonary infection with C. neoformans using a transgenic mouse expressing T cell receptor for chitin deacetylase 2, which is a major T cell antigen in this fungal pathogen. During the latent infection stage, the granulomatous lesions were developed in lungs, which contained multinucleated giant cells engulfing these fungi, and B cells and T cells expressing MCP-1 as well as macrophages expressing TNF-α were observed in these granulomas. Using this model, the immunological mechanisms for latent infection with C. neoformans and its reactivation under immunocompromised conditions will be expected to be unveiled.

Free Research Field

感染症内科学

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、この重要な臨床的課題へのアプローチを可能とする動物モデルの作成に成功した。さらに、本モデルを用いることで、潜伏感染時にみられる肉芽腫や多核巨細胞の形成・維持における免疫機序の一端を明らかに出来た。今後、より詳細な免疫機序を解明することで、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期待される。