Role of dendritic cells in bridging innate and adaptive immune responses during bacterial infection

• Project Area: Matrix of Infection Phenomena
• Project/Area Number: 18073015
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Keio University
• Principal Investigator: KOYASU Shigeo Keio University, 医学部, 教授 (90153684)
• Project Period (FY): 2006 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥84,000,000 (Direct Cost: ¥84,000,000); Fiscal Year 2010: ¥16,800,000 (Direct Cost: ¥16,800,000); Fiscal Year 2009: ¥16,800,000 (Direct Cost: ¥16,800,000); Fiscal Year 2008: ¥16,800,000 (Direct Cost: ¥16,800,000); Fiscal Year 2007: ¥16,800,000 (Direct Cost: ¥16,800,000); Fiscal Year 2006: ¥16,800,000 (Direct Cost: ¥16,800,000)
• Keywords: 消化管関連リンパ組織 / 上皮細胞 / 樹状細胞 / リステリア / ヘリコバクター / 侵入因子 / PI3キナーゼ / 免疫記憶 / 自然免疫 / 獲得免疫 / 粘膜免疫 / ノックアウトマウス / トランスジェニックマウス / 腸管上皮細胞 / PI3K / E-カドヘリン / 記憶細胞

Research Abstract

We examined in this study how immune responses are induced against bacterial infection in the gastrointestinal tract. Immune response against Helicobacter pylori results in gastritis. We showed that H. pylori is captured by dendritic cells in Peyer's patches in the intestine but not in the stomach. Listeria monocytogenes invades our body through intestine and causes food poisoning. We showed that the major site of L. monocytogenes invasion is Peyer's patches with the aid of a Lieterial protein named internalin B.

Research Products

• [Journal Article] Listerial invasion protein intemalin B promotes the entry into ileal Peyer's patches in vivo (2011)
  • Author(s): Chiba, S., Nagai, T., Hayashi, T., Baba, Y., Nagai, S., Koyasu, S.
  • Journal Title: Microbiol Immunol. 55 Pages: 123-129
• [Journal Article] Type 2 innate immune responses and the natural helper cell. (2011)
  • Author(s): Koyasu, S., Moro, K.
  • Journal Title: Immunology 132 Pages: 475-481
• [Journal Article] Innate Th2-type immune responses and the Natural Helper Cell, a newly identified lymphocyte population. (2011)
  • Author(s): Koyasu, S., Moro, K.
  • Journal Title: Curr.Opin.Allergy Clin.Immunol. 11 Pages: 109-114
• [Journal Article] Listerial invasion protein internalin B promotes the entry into ileal Peyer's patches in vivo. (2011)
  • Author(s): Chiba, S., et al.
  • Journal Title: Microbiol.Immunol. Volume: 55 Pages: 123-129
  • Peer Reviewed
• [Journal Article] Innate production of Th2 cytokines by adipose tissue-associated c-Kit^<+>Sca-1^<+> lymphoid cells. (2010)
  • Author(s): Moro, K., Yamada, T., Tanabe, M., Takeuchi, T., Ikawa, T., Kawamoto, H., Furusawa, J.-I., Ohtani, M., Fujii, H. Koyasu, S.
  • Journal Title: Nature 463 Pages: 540-544
• [Journal Article] Natural Helper Cells: a new player in the innate immune response against helminth infection. (2010)
  • Author(s): Koyasu, S., Moro, K., Tanabe, M., Takeuchi, T.
  • Journal Title: Adv.Immunol. 108 Pages: 21-44
• [Journal Article] Innate production of Th2 cytokines by adipose tissue-associated c-Kit^+Sca-1^+ lymphoid cells. (2010)
  • Author(s): Moro, K., et al.
  • Journal Title: Nature 463 Pages: 540-544
  • Peer Reviewed
• [Journal Article] Critical roles of NK and CD8^<+> T cells in distinct phases of CNS listeriosis. (2009)
  • Author(s): Hayashi, T., Nagai, S., Baba, Y., Ikeda, E., Kawase, T., Koyasu, S.
  • Journal Title: J. Immunol. 182 Pages: 6360-6368
• [Journal Article] The non-phosphorylated status of CagA is pivotal for Helicobacter pylori pathogenesis. (2009)
  • Author(s): Suzuki, M., Mimuro, H., Kiga, K., Fukumatsu, M., Ishijima, N., Morikawa, H., Nagai, H., Koyasu, S., Gilman, R.H., Kersulyte, D., Berg, D.E., Sasakawa, C.
  • Journal Title: Cell Host Microb. 5 Pages: 23-34
• [Journal Article] Critical roles of NK and CD8^+ T cells in distinct phases of CNS listeriosis. (2009)
  • Author(s): Hayashi, T., et al.
  • Journal Title: J.Immunol. 82 Pages: 6360-6368
  • Peer Reviewed
• [Journal Article] Critical roles of NK and CD8+ T cells in distinct phases of CNS listeriosis. (2009)
  • Author(s): Hayashi, T. Nagai, S., Baba, Y., Ikeda, E. Kawase, T. and Koyasu, S
  • Journal Title: J. Immunol (in press)
  • Peer Reviewed
• [Journal Article] Critical roles of NK and CDS+ T cells in distinct phases of CNS list eriosis (2009)
  • Author(s): Hayashi, T., et.al.
  • Journal Title: J. Immunol. (in press) 182
  • Peer Reviewed
• [Journal Article] The non-phosphorylated status of CagA is pivotal for Hellcoba cter py lad pathogenesis (2009)
  • Author(s): Suzuki, M., et.al.
  • Journal Title: Cell Host Microb 5 Pages: 23-34
  • Peer Reviewed
• [Journal Article] Critical role of class IA PI3K for c-Rel expression in B lymp hocytes (2009)
  • Author(s): Matsuda, S., et.al.
  • Journal Title: Blood 113 Pages: 1037-1044
  • Peer Reviewed
• [Journal Article] Critical role of dendritic cells in determining the Th1/Th2 balance and the disease outcome upon Leishmania major infection. (2008)
  • Author(s): Suzue, K., Kobayashi, S., Takeuchi, T., Suzuki, M., Koyasu, S.
  • Journal Title: Int.Immunol. 20 Pages: 337-343
• [Journal Article] Critical role of dendritic cells in determining the Th1/Th2 balance and the disease outcome upon Leishmania major infection. (2008)
  • Author(s): Suzue, K., Kobayashi, S., Takeuchi, T., Suzuki, M. and Koyasu, S
  • Journal Title: Int. Immunol 20 Pages: 337-343
  • Peer Reviewed
• [Journal Article] mTOR and GSK3 differentially regulate LPS-induced IL-12 pr oduction in dendritic cells (2008)
  • Author(s): Ohtani, M., et.al.
  • Journal Title: Blood 112 Pages: 635-643
  • Peer Reviewed
• [Journal Article] Critical role of dendritic cells in determining the Thl/Th2 balanceand the disease outcome upon Leishmania major infection. (2008)
  • Author(s): Suzue, K, et. al.
  • Journal Title: Int. Immunol. 20 Pages: 337-343
  • Peer Reviewed
• [Journal Article] Helicobacter pylori dampens gut epithelial self-renewal by inhibiting apoptosis, a bacterial strategy to enhance colonization of the stomach. (2007)
  • Author(s): Mimuro, H., Suzuki, T., Nagai, S., Rieder, G., Suzuki, M., Nagai, T., Fujita, Y., Nagamatsu, K., Ishijima, N., Koyasu, S., Haas, R., Sasakawa, C.
  • Journal Title: Cell Host Microbe 2 Pages: 250-263
• [Journal Article] Role of Peyer's patches in Helicobacter pylori-induced gastritis. (2007)
  • Author(s): Nagai, S., Mimuro, H., Yamada, T., Baba, Y., Moro, K., Nochi, T., Kiyono, H., Suzuki, T., Sasakawa, C., Koyasu, S.
  • Journal Title: Proc.Natl.Acad.Sci.USA 104 Pages: 8971-8976
• [Journal Article] Role of Peyer's patches in Helicobacter pylori-induced gastritis. (2007)
  • Author(s): Nagai, S., et. al.
  • Journal Title: Proc. Natl. Acad. Sd. USA 104 Pages: 8971-8976
  • Peer Reviewed
• [Journal Article] Helicobacter pylori dampens gut epithelial self-renewal by inhibiting apoptosis, a bacterial strategy to enhance colonization of the stomach. (2007)
  • Author(s): Mimuro, H., et. al.
  • Journal Title: Cell Host Microbe 2 Pages: 250-263
  • Peer Reviewed
• [Journal Article] The Pten/PI3K pathway governs the homeostasis of Vα14_1NKTcells (2007)
  • Author(s): Kishimoto, H., et. al.
  • Journal Title: Blood 15 Pages: 3316-3324
• [Journal Article] Impairment of T cell interactions with antigen-presenting cells by immunosuppressive drugs reveals involvement of calcineurin and NF-κB in immunological synapse formation (2007)
  • Author(s): Zeyda, M., et. al.
  • Journal Title: J. Leukoc. Biol. 81 Pages: 319-327
• [Journal Article] Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo. (2006)
  • Author(s): Ohteki, T., Tada, H., Ishida, K., Sato, T., Maki, C., Yamada, T., Hamuro, J. and Koyasu, S.
  • Journal Title: J. Exp. Med. 203 Pages: 2329-2338
  • Peer Reviewed
• [Journal Article] Essential roles of DC-derived IL-15 as a mediator ofinflammatory responses in vivo. (2006)
  • Author(s): Ohteki T., et. al.
  • Journal Title: J. Exp. Med. 203 Pages: 2329-2338
• [Journal Article] Phosphoinositide 3-kinase in nitric oxides synthesis inmacrophage: critical dimerizaiton of inducible nitric oxidesynthase (2006)
  • Author(s): Sakai, K., et. al.
  • Journal Title: J. Biol. Chem. 281 Pages: 17736-17742
• [Journal Article] TLR5-mediated PI3K activation negatively regulates flagellin-induced pro-inflammatory gene expression (2006)
  • Author(s): Yu, Y., et. al.
  • Journal Title: J. Immunol. 176 Pages: 6194-6201
• [Presentation] Natural helper cell : innate lymphocyte producing Th2 cytokines. Annual Meeting of the Austrian Society for Allergology and Immunology in co-operation with the national societies of Croatia (2010)
  • Author(s): Shigeo Koyasu.
  • Organizer: Czech Republic, Hungary, Slovakia and Slovenia
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2010-12-05
• [Presentation] Listerial invasion protein internalin B promote the entry into ileal Peyer's patches in vivo. (2010)
  • Author(s): Chiba, S., et al.
  • Organizer: The 10^<th> Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路夢舞台国際会議場(兵庫)
  • Year and Date: 2010-09-08
• [Presentation] Role of phosphoinositide 3-kinase on helper T cell differentiation in Hlicobacter pylori-induced gastritis. (2010)
  • Author(s): Shigenori Nagai, Yutaka Kurebayashi, Yukiko Baba, Shigeo Koyasu.
  • Organizer: The 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-25
• [Presentation] Role of intemalin B in the gastrointestinal infection of and host immune response to Listeria monocytogenes. (2010)
  • Author(s): Sayuri Chiba Takeshi Nagai, Shigeo Koyasu.
  • Organizer: The 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-25
• [Presentation] Role of internalin B in the gastrointestinal infection of and hostimmune response to Listeria monocytogenes. (2010)
  • Author(s): Chiba, S., et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸ポートピアホテル、神戸国際会議場(兵庫)
  • Year and Date: 2010-08-25
• [Presentation] Role of phosphoinositide 3-kinase on helper T cell differentiation in Hlicobacter pylori-induced gastritis. (2010)
  • Author(s): Nagai, S., et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸ポートピアホテル、神戸国際会議場(兵庫)
  • Year and Date: 2010-08-25
• [Presentation] Natural helper cell : a newly identified innate lymphocyte producing Th2 cytokines. (2010)
  • Author(s): Shigeo Koyasu.
  • Organizer: The 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 2010-08-24
• [Presentation] Natural helper cell : a newly identified innate lymphocyte producing Th2 cytokines. (2010)
  • Author(s): Koyasu. S.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸ポートピアホテル、神戸国際会議場(兵庫)
  • Year and Date: 2010-08-24
• [Presentation] リステリア腸管感染における病原因子Internalin Bの役割 (2009)
  • Author(s): 千葉紗由利, 永井重徳, 永井武, 小安重夫
  • Organizer: 第39回日本免疫学会総会・学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] リステリア腸管感染における病原因子Intemalin Bの役割. (2009)
  • Author(s): 千葉紗由利, 他
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-04
• [Presentation] マウス腸間膜に存在するnatural helper cellの自然免疫機構における役割. (2009)
  • Author(s): 茂呂和世, 他
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-02
• [Presentation] Role of dendritic cells in infectious immunity. (2009)
  • Author(s): Shigeo Koyasu.
  • Organizer: The 7^<th> Conference of the Federation of African Immunology Societies, Sharm El-Sheick
  • Place of Presentation: Egypt
  • Year and Date: 2009-11-04
• [Presentation] Role of internalin B, in the gastrointestinal infection with Listeriamonocytogenes. (2009)
  • Author(s): 千葉紗由利, 他
  • Organizer: 第9回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 淡路夢舞台国際会議場(兵庫)
  • Year and Date: 2009-09-09
• [Presentation] Critical role of IL-17A in helicobacter pylori-induced gastritis. (2009)
  • Author(s): Shigenori Nagai, T.Yamada, Y.Baba, Y.Iwakura, Shigeo Koyasu.
  • Organizer: The 9^<th> World Congress of Inflammation
  • Place of Presentation: 東京
  • Year and Date: 2009-07-08
• [Presentation] Critical roles of NK and CD8^+ T cells in central nervous system listeriosis. (2009)
  • Author(s): Hayashi, T., et al.
  • Organizer: 18^<th> Internatinal Symposium on Molecular Cell Biology of Macrophages 2009
  • Place of Presentation: KKRホテル金沢(石川)
  • Year and Date: 2009-07-03
• [Presentation] Nature helper cell in the mesentery. (2009)
  • Author(s): Koyasu, S., et al.
  • Organizer: Kyoto T Cell Conference 2009 International Workshop on T Lymphocytes
  • Place of Presentation: 京都大学芝蘭会館(京都)
  • Year and Date: 2009-06-04
• [Presentation] Host immune response against Helicobacter pylori infection. (2008)
  • Author(s): Shigeo Koyasu.
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Host immune response against Helicobacter pylori infection (2008)
  • Author(s): Koyasu, S
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会合同大会
  • Place of Presentation: 兵庫
  • Year and Date: 2008-12-12
• [Presentation] 中枢神経系リステリア感染症におけるIFNγとIL-17の役割 (2008)
  • Author(s): 林俊行, 永井重徳, 馬場夕紀子, 小安重夫
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] 中枢神経系リステリア感染症におけるIFNγとIL-17 の役割 (2008)
  • Author(s): 林俊行,永井重徳,馬場夕紀子,小安重夫
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] 中枢神経系リステリア感染症におけるIFNYとIL-17の役割 (2008)
  • Author(s): 林俊行, 他
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] ヘリコバクタービロリ感染による胃炎発症におけるIL-17Aの役割 (2008)
  • Author(s): 永井重徳, 山田健人, 馬場夕紀子, 岩倉洋一郎, 小安重夫
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] Immune reaction to Listeria monocytogenes in the brain (2008)
  • Author(s): 林俊行, 他
  • Organizer: 第8回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 兵庫
  • Year and Date: 2008-09-09
• [Presentation] The role of PI3K for the function of gastrointestinal mast cells. (2008)
  • Author(s): Shigeo Koyasu, Akiko Minowa, Satoshi Matsuda.
  • Organizer: The 27^<th> Symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Curacao, the Netherlands
  • Year and Date: 2008-05-02
• [Presentation] Analysis of functions of T cells on CNS listeriosis (2007)
  • Author(s): Hayashi, T, et. al
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Role of PI3K in immune receptor signaling (2007)
  • Author(s): Shigeo Koyasu
  • Organizer: The 13^<th> International Congress of Immunology
  • Place of Presentation: Rio de Janeiro, Brazil
  • Year and Date: 2007-08-25
• [Presentation] 胃炎発症における球状ヘリコバクターピロリの重要性 (2007)
  • Author(s): 永井重徳, 三室仁美, 山田健人, 馬場夕紀子, 茂呂和世, 鈴木敏彦, 笹川千尋, 小安重夫
  • Organizer: 第13回日本ヘリコバクター学会
  • Place of Presentation: 滋賀
  • Year and Date: 2007-06-22
• [Presentation] The role of coccoid form of Helicobacter pylori on the induction of gastritis. (2006)
  • Author(s): Shigenori Nagai, Hitomi Mimuro, Taketo Yamada, Yukiko Baba, Kazuyo Moro, Toshihiko Suzuki, Chihiro Sasakawa, Shigeo Koyasu.
  • Organizer: 第36回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2006-12-13
• [Presentation] The role of acquirec immunity on CNS listeriosis. (2006)
  • Author(s): Toshiyuki Hayashi, Shigenori Nagai, Yukikc Baba, Shigeo Kovasu.
  • Organizer: 第36回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2006-12-13
• [Remarks] ホームページ
  • URL: http://www.koyasu.umin.ne.jp/
• [Remarks]
  • URL: http://www.med.keio.ac.jp/rdb/gcoe-stemcell/view.php?i=13