Regulatory mechanism of the macrophage function by mycobacterial secretory components
| Project/Area Number |
24590522
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Kyoto University |
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Principal Investigator |
KAWAMURA Ikuo 京都大学, 医学(系)研究科(研究院), 准教授 (20214695)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 結核菌 / BCG / RD1 / カルパイン / マクロファージ / ASC / PD-1 / Tim-3 / サイトカイン / 免疫補助分子 / 感染防御 / T細胞 / JNK / Syk / IL-1a |
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| Outline of Final Research Achievements |
I have studied the molecular mechanism by which Mycobacterium tuberculosis (MTB) stimulates or regulates the host immune response. In the series of experiments I found that the region of difference 1 (RD1), a genomic locus in the MTB genome that has been shown to participate in the virulence of the bacterium, contributes to the maturation and secretion of IL-1α by enhancing the level of intracellular Ca2+ followed by calpain activation. Furthermore, it has been shown that the inflammasome adaptor ASC is phosphorylated at a 144-tyrosine residue during inflammasome activation in a Syk- and Jnk-dependent manner. Phosphorylated ASC forms speck-like aggregate and contributes to caspase-1 activation. In addition, it was found that PD-1 inhibitory signal severely affects the function of Th1 cells and Tim3-dependent signal is critical to regulation of the differentiation of memory T cell into effector T cells.
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] The RD1 locus in the Mycobacterium tuberculosis genome contributes to the maturation and secretion of IL-1α from infected macrophages through the elevation of cytoplasmic calcium levels and calpain activation.2014
Author(s)
Yang R, Xi C, Sita DR, Sakai S, Tsuchiya K, Hara H, Shen Y, Qu H, Fang R, Mitsuyama M, Kawamura I.
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Journal Title
Pathog Dis.
Volume: 70
Issue: 1
Pages: 51-60
DOI
Related Report
Peer Reviewed
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[Journal Article] Del Carmen Sasiain M. Two genetically-related multidrug-resistant Mycobacterium tuberculosis strains induce divergent outcomes of infection in two human macrophage models2013
Author(s)
Yokobori N, Lopez B, Geffner L, Sabio Y Garcia C, Schierloh P, Barrera L, de la Barrera S, Sakai S, Kawamura I, Mitsuyama M, Ritacco V
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Journal Title
Infect Genet Evol.
Volume: 16
Pages: 151-156
DOI
Related Report
Peer Reviewed
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