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Study on the molecular pathogenesis of opportunistic fungal infectious diseases in AIDS patients

Research Project

Project/Area Number 12670261
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionUniversity of the Ryukyus

Principal Investigator

KAWAKAMI Kazuyoshi  University of the Ryukyus, Faculty of Medicine, Associate professor, 医学部, 助教授 (10253973)

Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
KeywordsFungal infection / Cryptococcus / Penicillium marneffei / Innate immunity / NKT cells / γδT cells / オステオポンチン / エイズ / 日和見真菌感染症 / NK細胞 / IFN-_γ / IL-18 / IL-12 / IFN-gamma
Research Abstract

We have investigated the host defense mechanism against Cryptococcus neoformans infection using a mouse model to clarify the molecular mechanisms of opportunistic fungal infection complicated in AIDS. In this study, we evaluated the roles of innate immune lymphocytes, such as NK NKT and γδ T cells. NK and NKT cells accumulated in lung and regional lymphmode in a MCP-1-dependent manner after cryptococcal infection, while the accumulation of γδ T cells was not dependent of this chemokine. NKT cells were found to play an important role in the development of Th1-mediated host protection from this infection using mice genetically lacking Vα14 NKT cells. In contrast, γδ T cells were suggested to negatively regulate these responses, because the infection was improved in mice depleted of these cells by administration of ant-γδ TCR mAb. Further investigations are now under way. On the other hand, we also demonstrated in an in-vitro study using peripheral blood mononuclear cells the involvement of osteopontin in the IL-12-induced Th1 responses in infection with Penicillium marneffei, a major opportunistic fungal pathogen in AIDS patients in Southeast Asia. In the present study, we have approached the process reaching from innate to acquired immune responses during fungal infection, which may provide a basic implication in constructing the strategies for prevention and treatment against AIDS-related infection caused by these pathogens.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Kawakami, K.et al.: "Reduced host resistance and Th1 response to Cryptococcus neoformans in interleukin-18 deficient mice"FEMS Microbiology Letters. 186. 121-126 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.et al.: "IL-18 contributes to host resistance against infection with Cryptococcus neoformans in mice with defective IL-12 synthesis through induction of IFN-γ production by NK cells"Journal of Immunology. 165. 941-947 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.et al.: "NK cells eliminate Cryptococcus neoformans by potentiating the fungicidal activity of macrophages, rather than by direct killing them, upon stimulation with IL-12 and IL-18"Microbiology and Immunology. 44. 1043-1050 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.et al.: "Circulating soluble CD4 directly prevents host resistance and delayed-type hypersensitivity response to Cryptococcus neoformans in mice"Microbiology and Immunology. 44. 033-1041 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.et al.: "Activation of Vα14+ Natural Killer T Cells by α-Galactosylceramide Results in the Development of Th1 Response and Local Host Resistance in Mice Infected with Cryptococcus neoformans"Infection and Immunigy. 69. 213-220 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.et al.: "Enhanced IFN-γ Production through Activation of Vα14+ NKT Cells by α-galactosylceramide in Interleukin-18-Deficient Mice with Systemic Cryptococcosis"Infection and Immunity. 69. 6643-6650 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.et al.: "Monocyte chemoattractant protein-1-dependent increase of Vα14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection"Journal of Immunology. 167. 6525-6532 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koguchi, Y.et al.: "Penicillium marneffei causes osteopontin-mediated production of interleukin-12 by peripheral blood mononuclear cells"Infection and Immunity. 70. 1042-1048 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.et al.: "Anti-CD11b Monoclonal Antibody Suppresses Brain Dissemination of Cryptococcus neoformans in Mice"Microbiology and Immunology. 46. 181-186 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.: "Interleukin-18 and host defense against infections pathogens"Journal of Immunotherapy. 25. S12-S19 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koguchi, Y., Kawakami, K.: "Cryptococcal infection and Th_1-T_2 cytokine balance"International Review of Immunology. 21. 423-438 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.: "Role for natural killer T cells in host defense to cryptococcal infection"Reusta Iberoamericana Micologia. 19. 149-154 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 川上和義: "クリプトコッカス感染防御とNKT細胞:自然免疫から獲得免疫へ"日本医真菌学会雑誌. 43. 137-141 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K., Koguchi, Y., Qureshi, M. H., et al.: "Reduced host resistance and Th1 response to Cryptococcus neoformans in interleukin-18 deficient mice"FEMS Microbiology Lett.. 186. 121 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K., Koguchi, Y., Qureshi, M. H., et al.: "IL-18 contributes to host resistance against infection with Cryptococcus neoformans in mice with defective IL-12 synthesis through induction of IFN-γ production by NK cells"J. Immunol.. 165. 941 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K., Koguchi, Y., Qureshi, M. H., et al.: "Circulating soluble CD4 directly prevents host resistance and delayed-type hypersensitivity response to Cryptococcus neoformans in mice"Microbiol. Immunol.. 44. 1033 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K., Koguchi, Y., Qureshi, M. H., et al.: "NK cells eliminate Cryptococcus neoformans by potentiating the fungicidal activity of macrophages, rather than by directly killing them, upon stimulation with IL-12 and IL-18"Microbiol. Immunol.. 44. 1043 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K., Kinjo, Y., Yara, S., et al.: "Activation of Vα14+ natural killer T cells by α-galactosylceramide results in the development of Th1 response and local host resistance in mice infected with Cryptococcus neoformans"Infect. Immun.. 69. 213 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K., Kinjo, Y., Yara, S., et al.: "Enhanced IFN-γ production through activation of Vα14+ NKT cells by α-galactosylceramide in IL-18-deficient mice with systemic cryptococcosis"Infect. Immun.. 69. 6643 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K., Kinjo, Y., Uezu, K., et al.: "Monocyte chemoattractant protein-1-dependent increase of Vα14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection"J. Immunol.. 167. 6525 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koguchi, Y., Kawaguchi, K., Kon, S., et al.: "Penicillium marneffei causes osteopontin-mediated production of interleukin-12 by peripheral blood mononuclear cells"Infect. Immun.. 70. 1042 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K., Koguchi, Y., Qureshi, M. H., et al.: "Anti-CD11b monoclonal antibody suppresses brain dissemination of Cryptococcus neoformans in mice"Micobiol. Immunol.. 46. 181 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.: "Interleukin-18 and host defense against infectious pathogens"J. Immunotherapy. 25. S12 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koguchi, Y., and Kawakami, K.: "Cryptococcal infection and Th1-Th2 cytokine balance"Int. Rev. Immunol.. 21. 423 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.: "Role for natural killer T cells in host defense to cryptococcal infection"Revista Iberoamericana Micologia. 19. 149 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K.: "The role of natural killer T cells in host defense to cryptococcal infection. A bridge from innate to acquired immunity"Jpn. J. Med. Mycol.. 43. 137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami, K. et al.: "Anti-CD116 monoclonal antibody suppresses brain dissemination of Cryptococcus neoformans in mice"Microbiology and Immunology. 46. 181-186 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawakami, K. et al.: "Minimal contribution of Vα14 natural killer T cells to Th1 response and host resistance against mycobacterial infection in mice"Microbiology and Immunology. 46. 207-210 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koguchi, Y. et al.: "Penicillium marneffei causes osteopontin-mediated production of interleukin-12 by peripheral blood mononuclear cells"Infection and Immunity. 70. 1042-1048 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawakami, K.: "Interleukin-18 and host defense against infectious pathogens"Journal of Immunotherapy. 25. S12-S19 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawakami, K.: "Role of natural killer T cells in host defense against cryptococcal infection"Revista Iberoamericana de Micologia. 19. 149-154 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koguchi, Y.Kawakami, K.: "Cryptococcal infection and Th1-Th2 cytokine balance"International Review of Immunology. 21. 423-438 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawakami, K. et al.: "Monocytechemoattractant protein-1-dependent increase of Vα14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection"Journal of Immunology. 167. 6525-6532 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawakami, K. et al.: "Enhanced Gamma interferon production through activation of Vα14^+ natural killer T cells by α-Galactosylceramide in interleukin-18-deficient mice with systemic cryptococcosis"Infect ionand Immunity. 69. 6643-6650 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawakami, K. et al.: "Penicillium marneffei causes osteopontin-mediated production of interleukin-12 by peripheral blood mononuclear cells"Infection and Immunity. 70. 1042-1048 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koguchi, Y. et al.: "Minimal contribution of Vα14 natural killer T cells to Th1 response and host resistance against mycobacterial infection in mice"Microbiology and Immunology. 46(3)(印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawakami, K. et al.: "Anti-CD11b monoclonal antibody suppresses brain dissemination of cryptococcus neoformans in mice"Microbiology and Immunology. 46(3)(印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawakami, K.: "Interleukin-18 and host defense against infectious pathogens"Journal of Immuno therapy. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawakami,K. et al.: "Reduced host resistance and Th1 response to Cryptococcus neoformans in interleukin-18 deficient mice"FEMS Microbiology Letters. 186. 121-126 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawakami,K. et al.: "IL-18 contributes to host resistance against infection with Cryptococcus neoformans in mice with defective IL-12 synthesis through induction of IFN-γ production by NK Cells."Journal of Immunology. 165. 941-947 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe,K. et al.: "Th1-Th2 cytokino kinetics in the bronchoalveolar lavages fluid of mice infected with Cryptococcus neoformans of different virulences"Microbiology and Immunology. 44. 849-855 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawakami,K. et al.: "Circulating soluble CD4 directly prevents host resistance and delayed-type hypersensitivity response to Cryptococcus neoformans in mice"Microbiology and Immunology. 44. 1033-1041 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawakami,K. et al.: "NK cells eliminate Cryptococcus neoformans by potentiating the fungicidal activity of macrophages rather than by directly killing them upon stimulation with IL-12 and IL-18"Microbiology and Immunology. 44. 1043-1050 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawakami,K. et al.: "Activation of Val4^+ natural killer T cells by α-galactosyl ceramide results in development of Th1 response and local host resistance in mice infected with Cryptococcus neoformans"Infection and Immunity. 69. 213-220 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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