Bacterial internalization into cytosol-dependent caspase-1 activation in Listeria-infected murine macrophages

• Project/Area Number: 20590440
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Kyoto University
• Principal Investigator: NOMURA Takamasa Kyoto University, 人間生活学部, 講師 (40362529)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: リステリア / カスパーゼ / オートファジー / サイトカイン / 細胞内寄生菌 / マクロファージ / IL-1α / 細胞内カルシウムシグナル / エスケープ / 炎症性サイトカイン

Research Abstract

The mechanism of IL-1α/β production from Listeria monocytogenes-infected macrophages was elucidated. L. monocytogenes internalized into cytoplasmic space was recognized by AIM2 which was a pattern recognition receptor of host cells. Formation of inflammsome containing ASC was induced and activated the caspase-1 resulting to maturation of IL-1β In addition, bacterial entry into cytoplasm also activated calcium signaling pathway. Calcium signals should activate a Calcium-dependent protease,calpain resulting to IL-1α maturation and release of mature IL-1α/β by autophagy or secretary lysosome pathways.

Research Products

• [Journal Article] Involvement of absent in melanoma2 in inflammasome activation in macrophages infected with Listeria monocytogenes (2010)
  • Author(s): Tsuchiya K., Hara H., Kawamura I., Nomura T., Yamamoto T., Daim S., Dewamitta S.R., Shen Y., Fang R., Mitsuyama M.
  • Journal Title: Journal of Immunology. 185(2) Pages: 1186-1195
• [Journal Article] Toll-like receptor 2- and MyD88-dependent phosphatidylinositol 3-kinase and Rac1 activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophages. (2010)
  • Author(s): Shen Y., Kawamura I., Nomura T., Tsuchiya K., Hara H., Dewamitta S.R., Sakai S., Qu H., Daim S., Yamamoto T., Mitsuyama M.
  • Journal Title: Infection and Immunity 78(6) Pages: 2857-2867
  • NAID: 120002381103
• [Journal Article] Listeriolysin O-dependent bacterial entry into the cytoplasm is required for calpain activation and interleukin-1 alpha secretion in macrophages infected with Listeria monocytogenes. (2010)
  • Author(s): Dewamitta S.R., Nomura T., Kawamura I., Hara T., Tsuchiya K., Kurenuma T., Shen Y., Daim S., Yamamoto T., Qu T., Sakai S., Xu Y., Mitsuyama M.
  • Journal Title: Infection and Immunity. 78(5) Pages: 1884-18894
• [Journal Article] Involvement of absent in melanoma2 in inflammasome activation in macrophages infected with Listeria monocytogenes. (2010)
  • Author(s): Tsuchiya Kohsuke, Hara Hideki, Kawamura Ikuo, Nomura Takamasa, Yamamoto Takeshi, Daim Sylvia, Dewamitta Sita R., Shen Yanna, Mitsuyama Masao
  • Journal Title: Journal of Immunology Volume: 185(2) Pages: 1886-1995
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2- and MyD88-dependent phosphatidylinositol 3-kinase and Racl activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophages. (2010)
  • Author(s): Shen Yamma, Kawamura Ikuo, Nomura Takamasa, Tsuchiya Kousuke, Hara Hideki, Dewamitta Sita R., Sakai Shunsuke, Qu Huixin, Daim Sylvia, Yamamoto Takeshi, Mitsuyama Masao
  • Journal Title: Infection and Immunity Volume: 78(6) Pages: 2857-2867
  • Peer Reviewed
• [Journal Article] Listeriolysin O-dependent bacterial entry into the cytoplasm is required for calpain activation and interleukin-1 alpha secretion in macrophages infected with Listeria monocytogenes. (2010)
  • Author(s): Dewamitta SR, Nomura T, Kawamura I, Hara H, Tsuchiya K, Kurenuma T, Shen Y, Daim S, Yamamoto T, Qu H, Sakai S, Xu Y, Mitsuyama M.
  • Journal Title: Infection and Immunity 78(5) Pages: 1884-1994
  • Peer Reviewed
• [Journal Article] Dependency of caspase-1 activation induced in macrophages by Listeria monocytogenes on cytolysin, listeriolysin O, after evasion from phagosome into the cytoplasm. (2008)
  • Author(s): Hara H., Tsuchiya K., Nomura T., Kawamura I., Shoma S., Mitsuyama M.
  • Journal Title: Journal of Immunology 180(12) Pages: 7859-7868
• [Presentation] マクロファージのリステリア貪食能のTLR2による増幅 (2009)
  • Author(s): 野村卓正、申艶娜、土屋晃介、原英樹、酒井俊祐、屈慧新、河村伊久雄、光山正雄
  • Organizer: 第20回日本生体防御学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-25
• [Presentation] TLR2 signal is required for effective phagocytosis of Listeria monocytogenes by macrophages (2009)
  • Author(s): 野村卓正、申艶娜、土屋晃介、原英樹、酒井俊祐、屈慧新、河村伊久雄、光山正雄
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-03-12
• [Presentation] リステリアの細胞内動態がIL-1・産生誘導に及ぼす影響 (2008)
  • Author(s): 野村卓正、土屋晃介、原英樹、内山良介、河村伊久雄、光山正雄
  • Organizer: 第81回日本細菌学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-03-26
• [Presentation] リステリアの細胞内動態がIL-1・産生誘導に及ぼす影響 (2008)
  • Author(s): 野村卓正、土屋晃介、原英樹、内山良介、河村伊久雄、光山正雄
  • Organizer: 第7回感染症沖縄フォーラム
  • Place of Presentation: 沖縄
  • Year and Date: 2008-02-16
• [Remarks] ホームページ等