細胞内寄生性原虫の感染防御機構

• Project/Area Number: 19041046
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: 山本 雅裕 Osaka University, 医学系研究科, 助教 (00444521)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥8,500,000 (Direct Cost: ¥8,500,000); Fiscal Year 2008: ¥4,300,000 (Direct Cost: ¥4,300,000); Fiscal Year 2007: ¥4,200,000 (Direct Cost: ¥4,200,000)
• Keywords: TLR / シグナル伝達 / 転写因子 / 原虫感染免疫 / IFN-γ

Research Abstract

TLR非依存的にIFN-γが産生される分子機序について、T.cruzi感染により引き起こされる宿主の細胞内カルシウムイオンの濃度上昇が関与しているかどうかを検討する目的で、FK506を用いてカルシウムシグナルを阻害したところ、T.cruzi感染によるIFN-γ産生が減少した。また、FK506がカルシニューリンの阻害剤であることから、カルシニューリンの下流に存在するNFATc1のT.cruzi感染によるIFN-γ産生における役割について検討したところ、T.cruzi感染によりNFATc1が核移行し、さらにNFATc1欠損細胞においてはT.cruzi感染によるIFN-γ産生が減少した。さらに、NFATc1欠損樹状細胞はT.cruzi感染による活性化が著しく減弱した。以上のことから、T.cruzi感染後TLR非依存的にNFATc1を介して自然免疫担当細胞よりIFN-γが産生され宿主自然免疫応答が惹起されることが判明した。
これらの結果より、T.cruzi感染に対し宿主がTLR依存的・非依存的な自然免疫応答を引き起こす防御機構を有していることが明らかとなった。

Research Products

• [Journal Article] Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation (2009)
  • Author(s): Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T, Kamei K, Nakagawa T, Kato M, Murata S, Yamaoka S, Yamamoto M, et.al.
  • Journal Title: Nat Cell Biol. 11 Pages: 123-132
  • Peer Reviewed
• [Journal Article] Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium (2008)
  • Author(s): Saiga H, Nishimura J, Kuwata H, Okuyama M, Matsumoto S, Sato S, Matsumoto M, Akira S, Yoshikai Y, Honda K, Yamamoto M, Takeda K
  • Journal Title: J Immunol. 181 Pages: 8521-8527
  • Peer Reviewed
• [Journal Article] Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly (2008)
  • Author(s): Huen MS, Huang J, Yuan J, Yamamoto M, et.al.
  • Journal Title: Mol Cell Biol. 19 Pages: 6104-6112
  • Peer Reviewed
• [Journal Article] Stat6-independent tissue inflammation occurs selectively on the ocular surface and perioral skin of IkappaBzeta-/-mice (2008)
  • Author(s): Ueta M, Hamuro J, Ueda E, Katoh N, Yamamoto M, et.al.
  • Journal Title: Invest Ophthalmol Vis Sci. 46 Pages: 3387-3394
  • Peer Reviewed
• [Journal Article] Gene-specific requirement of a nuclear protein, IkappaB-zeta, for promoter association of inflammatory transcription regulators (2008)
  • Author(s): Yamazaki S, Matsuo S, Muta T, Yamamoto M, et.al.
  • Journal Title: J Biol Chem. 283 Pages: 32404-32411
  • Peer Reviewed
• [Journal Article] ATP drives lamina propria T(H)17 cell differentiation (2008)
  • Author(s): Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, et.al.
  • Journal Title: Nature. 455 Pages: 808-812
  • Peer Reviewed
• [Journal Article] Role of nuclear IkappaB proteins in the regulation of host immune responses (2008)
  • Author(s): Yamamoto M, Takeda K.
  • Journal Title: J Infect Chemother. 14 Pages: 265-269
  • Peer Reviewed
• [Journal Article] Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency. (2007)
  • Author(s): Yamamoto, M, et. al.
  • Journal Title: J Exp Med. 204 Pages: 2233-2239
  • Peer Reviewed
• [Journal Article] Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor-mediated immune responses but not in TCR signaling (2007)
  • Author(s): Kawagoe, T・Sato, S・Jung, A・Yamamoto, M, et. al.
  • Journal Title: J Exp Med. 204 Pages: 1013-1024
  • Peer Reviewed
• [Journal Article] FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor-associated kinase 1-MyD88 interaction. (2007)
  • Author(s): Zhande, R・Dauphinee, SM・Thomas, JA・Yamamoto, M, et. al.
  • Journal Title: Mol Cell Biol. 27 Pages: 7394-8404
  • Peer Reviewed
• [Presentation] 第二回原虫感染免疫研究会 (2009)
  • Author(s): 山本雅裕
  • Place of Presentation: 佐賀、日本
• [Presentation] Trib1 is a negative regulator of NF-IL6 in TLR signalling (2008)
  • Author(s): Masahiro, Yamamoto
  • Organizer: Keystone Symposia, Innate Immunity
  • Place of Presentation: Keystone 米国
  • Year and Date: 2008-02-27
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/yamamoto2.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/yamamoto2.html