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Possible involvement of M. bovis BCG-producing TLR2 ligand to generate protective immunity by inducing TH1 cytokine productions

Research Project

Project/Area Number 13670270
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KAWAMURA Ikuo  Kyoto Univ. Grad. Sch. Med. Assist. Prof., 医学研究科, 助手 (20214695)

Co-Investigator(Kenkyū-buntansha) MITSUYAMA Masao  Kyoto Univ. Grad. Sch. Med. Prof, 医学研究科, 教授 (10117260)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
KeywordsMycobacterium bovis BCG / Mycobacterium tuberculosis / Interleukin-12 / Interferon-γ / Toll-like receptor 2 / NF-kB / macrophages / Toll-like receptor / IL-18 / Toll様レセプター / CD14
Research Abstract

Among various inflammatory mediators produced at the early stage of infection, TH1 cytokines such as interferon-γ, interleukin 12 (IL-12) and IL-18 play a pivotal role for development of protective T cells. It is further known that the production of these cytokines is induced by viable, but not killed bacteria, which are capable of generating protective immunity. To identify the mycobacterial factor contributing to the TH1 cytokine productions, we prepared a culture filtrate from 1d-culture of viable BCG (vBCG) and measured the cytokine-inducing activity. The culture filtrate elicited IL-12p40 production from peritoneal macrophages. However, the similar preparation derived from killed BCG did not induce the cytokine production. The cytokine-inducing activity was detected in macrophages of C3H/HeJ mice and was not affected by E5531, LPS antagonist. Furthermore, the culture filtrate did not induce NF-κB activation in HEK293 cells transfected with TLR4 and MD-2. However, activation of the transcription factor was induced in cells transfected with TLR2 by stimulation with vBCG-derived culture filtrate. The cytokine-inducing activity was resistant to treatment with DNase and partially sensitive to treatment with proteinase K, suggesting that some proteinaceous and non-proteinaceous factors are involved in the cytokine production. The similar activity was also detected in the culture filtrate obtained from viable, but not killed M. tuberculosis H37Rv. These results suggest that the early secreted components from viable mycobacteria activate macrophages to produce IL-12 via TLR2 dependent pathway. It is likely that this is a critical interaction between bacteria and macrophages for the generation of protective immunity.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Kimoto, Terumi: "Differences in gamma interferon production induced by listeriolysin O and ivanolysin O result in different levels of protective immunity in mice infected with Listeria monocytogenes and Listeria ivanovii"Infection and Immunity. 71・5. 2447-2454 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito, Yutaka: "Seeligeriolysin O, a cholesterol-dependent cytolysin of Listeria seeligeri, induces gamma interferon from spleen cells of mice"Infection and Immunity. 71・1. 234-241 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nomura, Takamasa: "Essential role of interleukin-12 (IL-12) and IL-18 for gamma interferon production induced by listeriolysin O in mouse spleen cells"Infection and Immunity. 70・3. 1049-1055 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] kohda, Chikara: "Dissociated linkage of cytokine-inducing activity and cytotoxicity to different domains of listeriolysin O from Listeria monocytogenes"Infection and Immunity. 70・3. 1334-1341 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Baba, Hisashi: "Induction of gamma interferon and nitric oxide by truncated pneumolysin that lacks pore-forming activity"Infection and Immunity. 70・1. 107-113 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito, Yutaka: "Difference in cholesterol-binding and cytolytic activities between listeriolysin O and seeligeriolysin O : a possible role of alanine residue in tryptophan-rich undecapeptide"FEMS Microbiology Letters. 203. 185-189 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Baba, Hisashi: "Essential role of domain 4 of pneumolysin from Streptococcus pneumoniae in cytolytic activity as determined by truncated proteins"Biochemical and Biophysical Research Communications. 281. 37-44 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chitale, Sadhana: "Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry"Cellular Microbiology. 3・4. 247-254 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimoto, T. et al.: "Differences in gamma interferon production induced by listeriolysin O and ivanolysin O result in different levels of protective immunity in mice infected with Listeria monocytogenes and Listeria ivanovii"Infection and Immunity. 71. 2447-2454 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito, Y. et al.: "Seeligeriolysin O, a cholesterol-dependent cytolysin of Listeria seeligeri, induces gamma interferon from spleen cells of mice"Infection and Immunity. 71. 234-241 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nomura, T. et al.: "Essential role of interleukin-12 (IL-12) and IL-18 for gamma interferon production induced by listeriolysin O in mouse spleen cells"Infection and Immunity. 70. 1049-1055 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kohda, C. et al.: "Dissociated linkage of cytokine-inducing activity and cytotoxicity to different domains of listeriolysin O from Listeria monocytogenes"Infection and Immunity. 70. 1334-1341 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Baba, H. et al.: "Induction of gamma interferon and nitric oxide by truncated pneumolysin that lacks pore-forming activity"Infection and Immunity. 70. 107-113 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito, Y. et al.: "Difference in cholesterol-binding and cytolytic activities between listeriolysin O and seeligeriolysin O: a possible role of alanine residue in tryptophan-rich undecapeptide"FEMS Microbiology Letters. 203. 185-189 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Baba, H. et al.: "Essential role of domain 4 of pneumolysin from Streptococcus pneumoniae in cytolytic activity as determined by truncated proteins"Biophysical Research Communications. 281. 37-44 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chitale, S. et al.: "Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry"Cellular Microbiology. 3. 247-254 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishiguro, T. et al.: "Role of macrophage scavenger receptors in response to Listeria monocytogenes infection in mice. American Journal of Pathology 158: 179-188, 2001"American Journal of Pathology. 158. 179-188 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tachibana, T. et al.: "Sporothrix schenkii thermo-tolerant mutants losing fatal visceral infectivity but retaining high cutaneous infectivity"Medical Mycology. 39. 295-298 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yutaka Ito: "Seeligeriolysin O, a cholesterol-dependent cytolysin of Listeria seeligeri, induces gamma interferon from spleen cells of mice"Infection and Immunity. 71・1. 234-241 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Terumi Kimoto: "Differences in gamma interferon production induced by listeriolysin O and ivanolysin O result in different levels of protective immunity in mice infected with Listeria monocytogenes and Listeria ivanovil"Infection and Immunity. 71・5(In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yutaka Ito: "Difference in cholesterol-binding and cytolytic activities between listeriolysin O and seeligeriolysin O"FEMS Microbiology Letters. Vol.203. 185-189 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hisashi Baba: "Induction of gamma interferon and nitric oxide by truncated pneumolysin that lacks pore-forming activity"Infection and Immunity. Vol.70, No.1. 107-113 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takamasa Nomura: "Essential role of Interleukin-12 (IL-12) and IL-18 for gamma interferon production induced by listeriolysin O in mouse spleen cells"Infection and Immunity. Vol.70, No.3. 1049-1055 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Chikara Kohda: "Dissociated linkage of cytokine-inducing activity and cytotoxicity to different domains of listeriolysin O from Listeria monocytogenes"Infection and Immunity. Vol.70, No.3. 1334-1341 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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