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Determination of the critical region of listeriolysin O (LLO) for the cytokine-inducing activity and application of LLO to vaccination with killed BCG.

Research Project

Project/Area Number 11670263
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 University, Dept.Microbiol.Assist.Prof., 医学研究科, 助手 (20214695)

Co-Investigator(Kenkyū-buntansha) MITSUYAMA Masao  Kyoto University, Dept.Microbiol Professor, 医学研究科, 教授 (10117260)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordslisteriolysin O / IFN-γ / Mycobacterium bovis BCG / adjuvant / vaccine / tuberculosis / protective immunity / LPS / Listeria monocytogenes / NK細胞 / INF-γ / 感染防御免疫
Research Abstract

Listeriolysin O (LLO) is demonstrated to be a mojor virulence factor of Listeria monocytogenes and is one of the member of cholesterol-binding cytolysins. we have reported that LLO induces endogenous Th1-type cytokine productions independent of the membrane lytic activity. It suggests that LLO may play a role as an adjuvant to promote the generation of protective immunity if it does not exert the cytolytic activity in vivo. In the present study, therefore, we attempted to determine the critical region of LLO only for the cytokine-inducing activity and evaluated its effectiveness as an adjuvant by administration of LLO encapsulated with liposome containing cholesterol.
LLO deleted for the fourth domain (LLO415), which is important for expression of the cytolytic activity, showed IFN-γ inducing activity. However, recombinant fourth domain did not induce the cytokine production. The activity of LLO415 was considerably suppressed when the N-terminal portion was further deleted. These data indicated that the N-terminus of LLO but not C-terminal fourth domain is critical for the cytokine-inducing activity. The activity of LLO was not observed in spleen cells of C3H/HeJ mice and was blocked by anti-CD14 antibody, suggesting that the signal of LLO may transduce via a signaling pathway of LPS.Moreover, immunoprecipitation revealed that LLO bound to two molecules on J774.1 cells, of which molecular weights are approximately 50-60kDa. We believe that these molecules are involved in the signal transduction of LLO.
To determine the efficacy of LLO as an adjuvant, C3H/HeN mice were immunized with killed BCG along with LLO encapsulated in the liposome. The LLO showed no cytolytic activity and promoted generation of protective T cells, suggesting that LLO functions as the adjuvant to promote Th1-type host resistance. On the other hand, because LLO415 was not trapped in liposome well, the adjuvant activity was remained to be elucidated.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Tachibana,T.: "Involvement of CD4+ T cells and macrophages in acquired protection against infection with Sporothrix schenckii in mice."Med.Mycol.. 37. 397-404 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ebe,Y.: "The role of kupffer cells and regulation of neutrophil migration into the liver by macrophage inflammatory protein-2 in primary listeriosis in mice."Pathol.Int.. 49. 519-532 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Baba,H.: "Essential role of domain 4 of pneumolysin from Streptococcus pneumoniae in cytolytic activity as determined by truncated proteins."Biochem.Biophys.Res.Com.. 281. 37-44 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chitale,S.: "Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry."Cell.Microbiol.. 3. 247-254 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 河村伊久雄: "リステリア膜傷害毒素listeriolysin OによるTh1細胞の誘導"臨床免疫. 34. 153-160 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 河村伊久雄: "IL-12と細胞内寄生体感染"Biotherapy. 14. 675-680 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 河村伊久雄: "抗酸菌の細胞内感染の分子機構"化学療法の領域. 17(印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 光山正雄: "リステリアの膜傷害毒素と免疫系の相互作用"蛋白質、核酸、酵素. 46. 556-561 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 光山正雄: "別冊・医学のあゆみ、生体応答学の新展開 分担:感染とサイトカイン"医歯薬出版. 226 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 河村伊久雄: "マラリア学ラボマニュアル 分担:ELISPOT法によるインターロイキン産生細胞数の測定"菜根出版. 290 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 河村伊久雄: "結核 分担:結核菌のエスケープ機構と宿主免疫応答"医薬ジャーナル. 414 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 光山正雄: "結核 分担:結核と防御ワクチン"医薬ジャーナル. 414 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tachibana, T.: "Involvement of CD4+ T cells and macrophages in acquired protection against infection with Sporothrix schenkii in mice."Med.Mycol.. 37. 397-404 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ebe, Y.: "The role of kupffer cells and regulation of neutrohil migration into the liver by macrophage inflammatory protein-2 in primary listeriosis in mice."Pathol.Int.. 49. 519-532 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Baba, H.: "Essential role of domain 4 of pneumolysin from Streptococcus pneumoniae in cytolytic activity as determined by truncated proteins."Biochem.Biophys.Res.Com. 281. 37-44 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chitale, S.: "Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry."Cell.Microbiol. 3. 247-254 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 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)

    • Related Report
      2000 Annual Research Report
  • [Publications] Chitale,Sadana: "Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry"Cellular Microbiology. 3. 247-254 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 河村伊久雄: "抗酸菌の細胞内感染の分子機構"化学療法の領域. 17(発表予定). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 光山正雄: "リステリアの膜傷害毒素と免疫系の相互作用"蛋白質、核酸、酵素. 46. 556-561 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 河村伊久雄: "リステリア膜傷害毒素listeriolysin O によるTh1細胞の誘導"臨床免疫. 34. 153-160 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 河村伊久雄: "IL-12と細胞内寄生体感染"Biotherapy. 14. 675-680 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 河村伊久雄: "結核"医薬ジャーナル社. 414 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 河村伊久雄: "マラリア学ボマニュアル"菜根出版. 290 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ebe,Y.: "The role of Kupffer cells and regulation of neutrophil migration into the liver by a C-X-C chemokines in primary listeriosis"Pathology International. 49・4. 519-532 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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