Verification of hypothesis for reactivation-induced cryptococcosis and clarification of its immunological mechanism using an animal model
| Project/Area Number |
18H02851
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 54030:Infectious disease medicine-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| 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 / クリプトコックス症 / 動物モデル |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Production of IL-17A at innate immune phase leads to decreased Th1 immune response and attenuated host defense against infection with Cryptococcus deneoformans2020
Author(s)
Sato K, Yamamoto H, Nomura T, Kasamatsu J, Miyasaka T, Tanno D, Matsumoto I, Kagesawa T, Miyahara A, Zong T, Oniyama A, Kawamura K, Yokoyama R, Kitai Y, Ishizuka S, Kanno E, Tanno H, Suda H, Morita M, Yamamoto M, Iwakura Y, Ishii K, Kawakami K
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Journal Title
The Journal of Immunology
Volume: 205
Issue: 3
Pages: 686-698
DOI
Related Report
Peer Reviewed
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[Journal Article] Dectin-2-mediated signaling triggered by the cell wall polysaccharides of Cryptcoccus neoformans2019
Author(s)
Daiki Tanno, Rin Yokoyama, Kotone Kawamura, Yuki Kitai, Xiaoliang Yuan, Keiko Ishii, Magdia De Jesus, Hideki Yamamoto, Ko Sato, Tomomitsu Miyasaka, Hiroki Shimura, Nobuyuki Shibata, Yoshiyuki Adachi, Naohito Ohno, Sho Yamasaki, Kazuyoshi Kawakami
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Journal Title
Microbiology and Immunology
Volume: 63
Issue: 12
Pages: 500-512
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] クリプトコックス莢膜多糖成分によるDectin-2刺激経路の活性化2018
Author(s)
高野和希, 川村琴音, 丹野大樹, 中平絢子, 石井恵子, Magdia De Jesus, Arturo Casadevall, 安達禎之, 大野尚仁, 山崎 晶, 川上和義
Organizer
第29回日本生体防御学会学術総会
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