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Induction and regulation of Protective immune responses against malaria parasites

Research Project

Project/Area Number 16590340
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Parasitology (including Sanitary zoology)
Research InstitutionNagasaki University

Principal Investigator

YUI Katsuyuki  Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (90274638)

Co-Investigator(Kenkyū-buntansha) HONMA Kiri  Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (70307940)
MIYAKODA Mana  Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (30398151)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsmalaria / T cells / memory cells / dendritic cells / cytokine / macrophage / pattern recognition receptor / immune regulation / スポロゾイト / 防御免疫
Research Abstract

1.Modulation of T-cell immune responses by malaria parasites
We studied immune responses and the protective effect of CD4^+ T-cells in mice recovered from P.yoelii 17XNL infection. CD4^+ T-cells from spleen of mice recovered from malaria infection showed spesific proliferative responses. However, they produced limited levels of IL-2 and high levels of IL-10. Adoptive transfer of these purified CD4^+ T-cells could not confer protective immunity against sporozoite infection. These results suggested that CD4^+ T-cells in Plasmodium-infected mice are functionally modulated.
2.Function of dendritic cells in malaria-infected mice
We characterized function of dendritic cells from mice infected with P.yoelii. Production of IL-12 in response to Toll-like receptor stimulation was reduced when compared with normal dendritic cells while IL-10 production was augmented. The ability to activate antigen specific T-cells was not reduced in both MHC class I and class II pathways. We will continue to study molecular mechanisms underlying augmented IL-10 production and function of T-cells activated by these dendritic cells.
3.Function of IRF-4, transcription factor that regulates immune responses, in dendritic cells and macrophages
Transcription factor IRF-4 is expressed in immune cells including lymphocytes, dendritic cells and macrophages. We have revealed that IRF-4 plays a critical role for the differentiation of a subset of dendritic cells and has inhibitory role for the TLR-mediated signaling. This inhibition mainly regulates activation of MAP kinase JNK and NF-κB.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (10 results)

All 2005 2004

All Journal Article (10 results)

  • [Journal Article] Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS2005

    • Author(s)
      Kiri Honma et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102(44)

      Pages: 16001-16006

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Negative regulation of Toll-like-receptor signaling by IRF-42005

    • Author(s)
      Hideo Negishi et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102(44)

      Pages: 15989-15994

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interferon regulatory factor 4 negatively regulates the production of pro inflammatory cytokines by macrophages in response to LPS2005

    • Author(s)
      Kiri Honma et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102

      Pages: 16001-16006

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Negative regulation of Toll-like-receptor signaling by IRF-42005

    • Author(s)
      Hideo Negishi et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102

      Pages: 15989-15994

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS2005

    • Author(s)
      Kiri Honma et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 102(44)

      Pages: 16001-16006

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Negative regulation of Toll-like-receptor signaling by IRF-42005

    • Author(s)
      Hideo Negishi et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 102(44)

      Pages: 15989-15994

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hsp-antigen fusion and their use for immunization2004

    • Author(s)
      H.Udono et al.
    • Journal Title

      Methods 32

      Pages: 21-24

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Critical roles of interferon regulatory factor-4 in CD11B^high CD8α^- dendritic cell development2004

    • Author(s)
      S.Suzuki et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA. 101

      Pages: 8981-8986

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Critical roles of interferon regulatory factor-4 in CD11b^<high>CD8α^- dendritic cell development2004

    • Author(s)
      S.Suzuki et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 101

      Pages: 8981-8986

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Critical roles of interferon regulatory factor-4 in CD11b^<high>CD8a^- dendritic cell development2004

    • Author(s)
      S.Suzuki et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101

      Pages: 8981-8986

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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