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Immunological and genetic regulations of innate immunity against cutaneous leishmaniasis in mice

Research Project

Project/Area Number 06454202
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 寄生虫学(含医用動物学)
Research InstitutionJikei University School of Medicine

Principal Investigator

OHTOMO Hiroshi  Jikei University School of Medicine, Department of Tropical Medicine, Professor, 医学部, 教授 (80072916)

Co-Investigator(Kenkyū-buntansha) SAITO Saburo  Jikei University School of Medicine, Institute of DNA medicine, Lecturer, 医学部, 講師 (10186934)
MAKIOKA Asao  Jikei University School of Medicine, Department of Tropical Medicine, Lecturer, 医学部, 講師 (90119850)
KATAKURA Ken  Jikei University School of Medicine, Department of Tropical Medicine, Lecturer, 医学部, 講師 (10130155)
WATANABE Naohiro  Jikei University School of Medicine, Department of Tropical Medicine, Associate, 医学部, 助教授 (00057019)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1994: ¥4,500,000 (Direct Cost: ¥4,500,000)
Keywordscutaneous leishmaniasis / Leishmania amazonensis / innate immunity / resistant gene to infection / gene mapping / mouse / immunology / cytokines / nerve growth factor / 皮膚リーシュマニア / 感染抵抗性 / 遺伝子 / マッピング / NK細胞 / 肥満細胞 / γδT細胞
Research Abstract

This study was aimed to understand mechanisms of innate immunity against cutaneous leishmaniasis by examining immunological and genetic regulations in mice infected with Leishmania amazonensis, a pathogen of cutaneous leishmaniasis in the South America. Different strains of mice were subcutaneously inoculated with L.amazonensis promastigotes at the tail base and the size of the skin lesions was measured. Almost all strains of mice such as BALB/c and C57BL/6 exhibited susceptible phenotype to the infection, but SJL/J mice showed strong resistant phenotype without visual lesions. In crossing experiments, both male and female mice of (BALB/c x SJL/J) F1 produced intermediate lesions in size and the backcrossed mice (N2) exhibited susceptible and resistant phenotype at a ratio of approximately 1 : 1, suggesting that the onset of cutaneous lesion is regulated by a single autosomal gene. Mapping of the resistant gene was attempted by analyzing microsatellite DNA polymorphisms in a total of seventy-two N2 mice. The linkage analysis indicated that resistance phenotype of the N2 mice was not linked to Scl1, Scl2 and Lsh/Bcg/Ita gene, which have been reported as the disease control genes for L.major, L.mexicana and L.donovani infection, respectively. The experiments of immunological regulation using mast cell-deficient W/W^V mice, gene-targeted gamma/delta T cell-deficient mice and anti-asialo GM1-inoculated mice suggested that the natural resistance against L.amazonensis infection may be regulated by natural killer cells and gamma/delta T lymphocytes but not by mast cells. Furthermore, intracellular survival of Leishmania in macrophages might be controlled by nerve growth factor, a cytokine involving in inflammatory reactions.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] 大友弘士: "微生物のVIRULENCE.原虫" Clinical Infection and Chemotherapy. 1. 38-41 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 片倉賢: "リーシュマニア症の薬物療法とリーシュマニアの薬剤耐性" メディヤサークル. 40. 285-293 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saito, S.: "Eosinophil chemotactic activity in Leishmania amazonensis promastigotes." Parasitology Research. 82. 485-489 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Susaki, Y.: "Functional properties of murine macrophages promoted by nerve growth factor." Blood. 88. 4630-4637 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hamada, A.: "Nerve growth factor enhances survival and cytotoxic activity of human eosinophils" British Journal of Heamotology. 93. 299-302 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 渡辺直煕: "寄生虫感染防御におけるIgE" アレルギー科. 1. 535-539 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohtomo, H.and Katakura, K: "Virulence of microorganisms" parasitic protozoa. Clinical Infection and Chemotherapy in Japanese. 1. 38-41 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Katakura, K.and Ohtomo, H: "Chemotherapy of leishmaniasis and drug-resistance in Leishmania in Japanese" Media-Circle. 40. 285-293 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saito, S., Hamada, A., Watanabe, N., Obata, T., Katakura, K.and Ohtomo, H: "Eosinophil chemotactic activity in Leishmania amazonensis promastigotes" Parasitol Res. 82. 485-489 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Susaki, Y., Shimizu, S., Katakura, K., Watanabe, N., Kawamoto, K., Matsumoto, M., Tsudzuki, M., Furusaka, T., Kitamura, Y.and Matsuda, H: "Functional properties of murine macrophages promoted by nerve growth factor" Blood. 88. 4630-4637 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hamada, A., Watanabe, N., Ohtomo, H.and Matsuda, H: "Nerve growth factor enhances survival and cytotoxic activity to human eosinophils" Brit.J.Haematol. 93. 299-302 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Watanabe, N: "Role of IgE in protection to parasites in Japanese" Allergology. 1. 535-539 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saito,S.: "Eosinophil chemotactic activity in Leishmania amazonensis promastigotes." Parasitology Research. 82. 485-489 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Susaki,Y.: "Functional properties of murine macrophages promoted by nerve growth factor." Blood. 88. 4630-4637 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hamada,A.: "Nerve growth factor enhances survival and cytotoxic activity of human eosinohils." British Journal of Heamotology. 93. 299-302 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 渡辺直煕: "寄生虫感染防御におけるIgE" アレルギー科. 1. 535-539 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大友弘士: "微生物のVIRULENCE.原虫" Clinical Infection and Chemotherapy. 1. 38-41 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 片倉賢: "リーシュマニア症の薬物療法とリーシュマニアの薬剤耐性" メディヤサークル. 40. 285-293 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saito, S.: "Eosinophil chemotactic activity in Leishmania amazonensis promastigotes." Parasitology Research. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] 大友弘士: "微生物のVisulence原虫" Clinical Infection and Chemotherapy. 1. 38-41 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Katakura,K.: "Karyotype similarity of Leishmania isoltes from patients,sandflies and domestic dogs,identifying the major L.mexicana strain as an agent of cutaneous leishmaniasis in the Ecuadorian Andes." Studies on New World leishmaniasis and its transmition,with paticular reference to Ecador,Res.Rep.Ser.4. 4-8 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 片倉 賢: "リーシュマニア症の薬物療法とリーシュマニアの薬剤耐性" メディアサークル. (印刷中). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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