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Analysis of phagosome-associated protein (TACO) involved in the intracellular infection of mycobacterium

Research Project

Project/Area Number 13670207
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

NAITO Makoto  NIIGATA UNIVERSITY Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (30045786)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Takashi  Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (70313517)
HASEGAWA Go  Graduate School of Medical and Dental Sciences, Lecturer, 大学院・医歯学総合研究科, 講師 (90251800)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsmacrophages / TACO / intracellular transport protein / BCG / Listeria / transgenic mice
Research Abstract

Mycobacteria are intracellular pathogens that can survive within macrophage phagosomes. The molecular mechanisms involved in mycobacterial entry are still poorly characterized. We have identified a WD repeat host protein that was recruited to and actively retained on phagosomes by living, but not dead, mycobacteria. This protein, termed TACO, represents a component of the phagosome coat that is normally released prior to phagosome fusion with or maturation into lysosomes. In macrophages lacking TACO, mycobacteria were readily transported to lysosomes followed by their degradation. Expression of TACO in nonmacrophages prevented lysosomal delivery of mycobacteria and prolonged their intracellular survival. Active retention of TACO on phagosomes by living mycobacteria thus represents a mechanism preventing cargo delivery to lysosomes, allowing mycobacteria to survive within macrophages.
We have examined Listeria monocytogenesinfection murine models. As demonstrated by BCGinfection models, … More the expression of TACO was induced in macrophages by Listeria infection, suggesting that TACO is involved in the infection by intracellular parasites such as Listeria as well as BCG. However, IFN-gamma stimulation facilitated expression of TACO, indicating that upregulation of TACO expression might be secondary to inflammatory changes. Therefore we focused on BCGinfection models.
We employed TACOtransgenic mice produced by our collaborator, Prof. J Peters in Basel University. Previous data suggested that enhanced expression of TACO may downregulate phagosome-lysosome fusion and may provide disadvantageous effects for infection. Unexpectedly, the numbers of hepatic granulomas in TACO transgenic mice were smaller than those in wild type mice, indicating that transgenic mice were more resistant to BCG infection. Because TACO is a coat protein of phagosomes and closely related to actin fibers, TACO may be involved in not only in the transport of phagosomes but also endocytic function of macrophages. Further studies are undertaken to clarify the function of TACO. Less

Report

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

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kuwata K et al.: "AIM inhibits apoptosis of T cells and NKT cells in Corynebacterium-induced granuloma formation in mice"Am J Pathol. 162(3). 837-847 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saiura A et al.: "Detection of an up-regulation of a group of chemokine geness in murine cardiac allograft in the absence of interferon-γ by means of DNA microarray"Transplantation. 73(9). 1480-1486 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka T et al.: "The generation of monoclonal antibodies against human peroxisome proliferator-activated receptors (PPARs)"Atheroscl Thromb. 9(5). 233-242 (2002)

    • Description
      「研究成果報告書概要(和文)」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"Am J Pathol. 158(1). 179-188 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneyama H et al.: "Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease"J Exp Med. 193(1). 35-49 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuwata K, et al.: "AIM inhibits apoptosis of T cells and NKT cells in Corynebacterium-induced granuloma formation in mice"Am J Pathol. 162 (3). 837-847 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saiura A, et al.: "Detection of an up-regulation of a group of chemokine genes in murine cardiac allograft in the absence of interferon-γ by DNA microarray"Transplantation. 73 (9). 1480-1486 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka T, et al.: "The generation of monoclonal antibodies against human peroxisome proliferator-activated receptors (PPARs)"Atheroscl Thromb. 9 (5). 233-242 (2002)

    • 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"Am J Pathol. 158 (1). 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] Yoneyama H, et al.: "Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease"J Exp Med. 193 (1). 35-49 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuwata K, et al.: "AIM inhibits apoptosis of T cells and NKT cells in Corynebacterium-induced granuloma formation in mice"Am J Pathol. 162(3)(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saiura A, et al.: "Detection of an up-regulation of a group of chemokine geness in murine cardiac allograft in the absence of interferon-γ by means of DNA microarray"Transplantation. 73(9). 1480-1486 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka T, et al.: "The generation of monoclonal antibodies against human peroxisome proliferator-activated receptors (PPARs)"Atheroscl Thromb. 9(5). 233-242 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishiguro T, Naito M, Yamamoto T, Hasegawa G, Gejo F, et al.: "Role of macrophage scavenger receptors in response to Listeria monocytogenes infection in mice"Am J Pathol. 158(1). 179-188 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoneyama H, Matsuno K, Zhang Y, Murai M, Itakura M, et al.: "Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease"J Exp Med. 193(1). 35-49 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高橋 潔, 内藤眞, 竹屋元裕: "生命を支えるマクロファージ"文光堂(東京). 542 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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