Study on the reactivation-induced development of AIDS-related cryptococcosis using a mouse model

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390263
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Tohoku University
• Principal Investigator: KAWAKAMI Kazuyoshi 東北大学, 医学(系)研究科(研究院), 教授 (10253973)
• Co-Investigator(Renkei-kenkyūsha): ISHII Keiko 東北大学, 大学院・医学系研究科, 准教授 (00291253)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: クリプトコックス / 内因性再燃 / エイズ / 免疫記憶 / メモリーT細胞 / 自然免疫

Research Abstract

Cryptococcus neoformans is an important opportunistic fungal pathogen, which causes severe meningoencephalitis in AIDS patients. Recently, it has been thought that cryptococcosis develops by reactivation of persistently infected pathogen under an immunocompromised condition. In this study, we examined the kinetics of memory T (Tm) cells in the infected lungs using a mouse model with persistent infection with C. neoformans. In addition, we succeeded in establishing a novel transgenic mouse expressing T cell receptor which recognizes MP98, a major T cell antigen of this fungal pathogen. In this mouse, both IFN-gamma synthesis and clearance of C. neoformans were strikingly accelerated in the lungs after infection. This makes it possible to more accurately examine the kinetics of Tm cells and the effect on the Tm cell response during reactivation of persistently infected C. neoformans.

Research Products

• [Journal Article] Defect of CARD9 leads to impaired accumulation of IFN-γ -producing memory-phenotype T cells in lungs and increased susceptibility to pulmonary infection with Cryptococcus neoformans (2014)
  • Author(s): Yamamoto H, Nakamura Y, Sato K, Takahashi Y, Nomura T, Miyasaka T, Ishii K, Hara H, Yamamoto N, Kanno E, Iwakura Y, Kawakami K
  • Journal Title: Infect. Immun Volume: 82 Pages: 1606-1615
  • DOI: 10.1128/IAI.01089-13
  • Peer Reviewed
• [Journal Article] クリプトコックス症の診断と治療, 深在性真菌症を学ぶ (2014)
  • Author(s): 川上和義
  • Journal Title: 臨床検査 Volume: 58 Pages: 90-96
  • URL: https://www.igakushoin.co.jp/journalDetail.do?journal=35841
• [Journal Article] 真菌感染における自然免疫活性化の分子機構 (2014)
  • Author(s): 石井恵子, 川上和義
  • Journal Title: 化学と生物(日本農芸化学会) Volume: 52 Pages: 83-89
  • URL: http://www.jsbba.or.jp/pub/journal_kasei/kasei_contents/vol52_2_2014.html
• [Journal Article] 真菌に対する免疫学的防御機構 (2013)
  • Author(s): 石井恵子, 川上和義
  • Journal Title: 臨床免疫・アレルギー科 Volume: 60 Pages: 411-418
  • URL: http://www.kahyo.com/item/M201310-604
• [Journal Article] Cryptococcus neoformans 感染におけるパターン認識と感染防御 (2012)
  • Author(s): 石井恵子, 川上和義
  • Journal Title: 日本医真菌学会雑誌 Volume: 53 Pages: 247-254
  • URL: https://www.jstage.jst.go.jp/article/mmj/53/4/53_247/_article
  • Peer Reviewed
• [Journal Article] TLR9-dependent activation of bone marrow-derived dendritic cells by URA5 DNA from Cryptococcus neoformans (2012)
  • Author(s): Tanaka M, Ishii K, Nakamura Y, Miyazato A, Maki A, Abe Y, Miyasaka T, Yamamoto H, Akahori Y, Fue M, Takahashi Y, Kanno E, Maruyama R, Kawakami K
  • Journal Title: Infect. Immun Volume: 80 Pages: 778-786
  • DOI: 10.1128/IAI.05570-11
  • Peer Reviewed
• [Presentation] Generation of transgenic mice expressing TCRα β specific for mannoprotein from Cyptococcus neoformans (2013)
  • Author(s): Matsumura K, Ishii K, Miyamura N, Nakamura Y, Tamura T, Kawakami K
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 20131211-13
• [Presentation] CARD9-mediated innate IFN-γ production and host defense to cryptococcal infection : involvement of memoryphenotype T cells (2013)
  • Author(s): Yamamoto H, Nakamura Y, Sato K, Matsumura K, Ishii K, Hara H, Kawakami K
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 20131211-13
• [Presentation] C-type lectin receptors and memory T cell response in cryptococcal infection (2013)
  • Author(s): Kawakami K
  • Organizer: Gordon Research Conference
  • Place of Presentation: Galveston, TX, USA
  • Year and Date: 20130113-18
• [Presentation] Memory T cells response after infection with Cryptococcus neoformans in mice (2012)
  • Author(s): Nakamura Y, Sato K, Yamamoto H, Ishii K, Kawakami K
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 20121205-07
• [Presentation] Role of Card9-mediated signaling in innate-phase IFN-γ production and Th17 differentiation in the host defense to cryptococcal infection (2012)
  • Author(s): Yamamoto H, Nakamura Y, Sato K, Matsumura K, Yamamoto N, Ishii K, Hara H, Kawakami K
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 20121205-07
• [Presentation] Effect of Dectin-2 deficiency on the host inflammatory response during infection with Cryptococcus neoformans (2012)
  • Author(s): Matsumura K, Yamamoto H, Nakamura Y, Sato K, Ishii K, Saijo S, Iwakura Y, Kawakami K
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 20121205-07
• [Presentation] CARD9欠損によるクリプトコックス感染の増悪機序 (2012)
  • Author(s): 佐藤光, 山本秀輝, 中村優里, 石井恵子, 松村香菜, 館正弘, 原博満, 川上和義
  • Organizer: 第23回日本生体防御学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 20120709-11
• [Presentation] Signaling via an adapter molecule CARD9 is essential for the host defense to infection with Cryptococcus neoformans (2012)
  • Author(s): Yamamoto H, Nakamura Y, Takahashi Y, Sato K, Yamamoto N, Ishii K, Hara H, Kawakami K
  • Organizer: 99th Annual Meeting, American Association of Immunologists
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 20120504-08
• [Presentation] Indispensable role for an adaptor molecule, CARD9 in the host defense against infection with Cryptococcus neoformans (2011)
  • Author(s): Yamamoto H, Yamamoto N, Nakamura Y, Ishii K, Hara H, Yamasaki S, Kawakami K
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 20111127-29