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Regulatory mechanism of the macrophage function by mycobacterial secretory components

Research Project

Project/Area Number 24590522
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionKyoto University

Principal Investigator

KAWAMURA Ikuo  京都大学, 医学(系)研究科(研究院), 准教授 (20214695)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
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)
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
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.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (28 results)

All 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 5 results) Presentation (17 results) (of which Invited: 1 results) Remarks (3 results)

  • [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.
    • Journal Title

      Pathog Dis.

      Volume: 70 Issue: 1 Pages: 51-60

    • DOI

      10.1111/2049-632x.12075

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 抗酸菌に対する宿主応答とサイトカインネットワーク2014

    • Author(s)
      河村伊久雄
    • Journal Title

      呼吸器内科

      Volume: 26 Pages: 42-48

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Phosphorylation of the adaptor ASC acts as a molecular switch that controls the formation of speck-like aggregates and inflammasome activity.2013

    • Author(s)
      Hara H, Tsuchiya K, Kawamura I, Fang R, Hernandez-Cuellar E, Shen Y, Mizuguchi J, Schweighoffer E, Tybulewicz V, Mitsuyama M.
    • Journal Title

      Nat Immunol.

      Volume: 14 Issue: 12 Pages: 1247-1255

    • DOI

      10.1038/ni.2749

    • NAID

      120005348332

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [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
    • Journal Title

      Infect Genet Evol.

      Volume: 16 Pages: 151-156

    • DOI

      10.1016/j.meegid.2013.01.007

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 結核菌に対する免疫応答調節機構2013

    • Author(s)
      河村伊久雄
    • Journal Title

      医学のあゆみ

      Volume: 246 Pages: 489-494

    • Related Report
      2013 Research-status Report
  • [Journal Article] 結核菌による宿主感染防御の発現制御2013

    • Author(s)
      河村伊久雄
    • Journal Title

      Kekkaku

      Volume: 88 Pages: 315-321

    • Related Report
      2012 Research-status Report
  • [Journal Article] Nitric oxide inhibits the NLRP3 inflammasome2012

    • Author(s)
      Hernandez-Cuellar E, Tsuchiya K, Hara H, Fang R, Sakai S, Kawamura I, Akira S, Mitsuyama M
    • Journal Title

      J Immunol.

      Volume: 189 Issue: 11 Pages: 2012-2012

    • DOI

      10.4049/jimmunol.1202479

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mice Deficient in Ficolin, a Lectin Complement Pathway Recognition Molecule, Are Susceptible to Streptococcus pneumoniae Infection2012

    • Author(s)
      Endo Y, et al.
    • Journal Title

      J Immunol

      Volume: 189 Issue: 12 Pages: 5860-5866

    • DOI

      10.4049/jimmunol.1200836

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 抗結核感染防御におけるASCの重要性について2014

    • Author(s)
      河村伊久雄
    • Organizer
      第84回実験結核研究会
    • Place of Presentation
      岐阜市長良川国際会議場
    • Year and Date
      2014-05-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Blockade of PD-1 signal pathway causes exacerbation of Mycobacterium tuberculosis infection via excessive IFN-γ production by antigen-specific CD4+ T cells.2014

    • Author(s)
      I. Kawamura.
    • Organizer
      16th International Conference on Emerging Infectious Diseases in the Pacific Rim. Acute Respiratory Infectious (ARI), Tuberculosis and Leprosy Panel Meeting.
    • Place of Presentation
      Dhaka, Bangladesh.
    • Related Report
      2013 Research-status Report
  • [Presentation] The impact of PD-1 inhibitory signal on the resistance to Mycobacterium tuberculosis infection.2014

    • Author(s)
      河村伊久雄
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Blockade of PD-1 signal pathway causes exacerbation of Mycobacterium tuberculosis infection via excessive IFN-γ production by antigen-specific Th1 type CD4+ T cells.2013

    • Author(s)
      I. Kawamura, S. Sakai and M. Mitsuyama.
    • Organizer
      US-Japan Cooperative Medical Science Program: Tuberculosis and Leprosy Panel Meeting in Japan.
    • Place of Presentation
      Sapporo, Japan.
    • Related Report
      2013 Research-status Report
  • [Presentation] 結核菌に対する宿主感染防御の発現制御2013

    • Author(s)
      河村伊久雄
    • Organizer
      第86回日本ハンセン病学会総会・学術大会
    • Place of Presentation
      さいたま市
    • Related Report
      2013 Research-status Report
  • [Presentation] Blockade of PD-1 signal pathway causes exacerbation of Mycobacterium tuberculosis infection via excessive IFN-γ production by antigen-specific Th1 type CD4+ T cells.2013

    • Author(s)
      I. Kawamura and M. Mitsuyama.
    • Organizer
      15th International Congress of Immunology.
    • Place of Presentation
      Milan, Italy.
    • Related Report
      2013 Research-status Report
  • [Presentation] The Thr223 in listeriolysin O is essential for the ability to induce the inflammasome activation2013

    • Author(s)
      Hara, H. et al.
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      幕張メッセ国際会議場(千葉市)
    • Related Report
      2012 Research-status Report
  • [Presentation] The role of listeriolysin O in calpain activation in Listeria monocytogenes-infected macrophages2013

    • Author(s)
      Qu, H. et al.
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      幕張メッセ国際会議場(千葉市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Role for NLRP3 and ASC in Streptococcus pneumoniae infection2013

    • Author(s)
      Tsuchiya, K. et al.
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      幕張メッセ国際会議場(千葉市)
    • Related Report
      2012 Research-status Report
  • [Presentation] PD-1シグナル経路による抗結核防御免疫の制御

    • Author(s)
      河村伊久雄
    • Organizer
      第82回実験結核研究会
    • Place of Presentation
      広島国際会議場(広島市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 結核菌による宿主感染防御の発現制御

    • Author(s)
      河村伊久雄
    • Organizer
      第87回日本結核病学会
    • Place of Presentation
      広島国際会議場(広島市)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] リステリア感染における主要病原因子listeriolysin O依存的なインフラマソーム応答の役割

    • Author(s)
      原英樹
    • Organizer
      第23回日本生体防御学会学術総会
    • Place of Presentation
      品川区総合区民会館(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] Nitric oxide inhibits the NLRP3 inflammasome

    • Author(s)
      Hernandez-Cuellar, E. et al.
    • Organizer
      第65回日本細菌学会関西支部総会
    • Place of Presentation
      臨床研究情報センター(神戸市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Critical role of listeriolysin O in clpain activation, which is triggered after evasion of Listeria monocytogenes from the phagosome into the cytoplasm of infected macrophages

    • Author(s)
      Qu, H. et al.
    • Organizer
      第65回日本細菌学会関西支部総会
    • Place of Presentation
      臨床研究情報センター(神戸市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Involvement of the domain 3 of listeriolysin O in inflammasome activation induced by Listeria monocytogenes infection

    • Author(s)
      Hara, H. et al.
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Nitric oxide-dependent suppression of the NLRP3 inflammasome activation

    • Author(s)
      Hernandez-Cuellar, E. et al.
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Related Report
      2012 Research-status Report
  • [Presentation] The inflammasome adaptor ASC plays a host-detrimental role in lethal infection with Listeria monocytogenes

    • Author(s)
      Tsuchiya, K. et al.
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Related Report
      2012 Research-status Report
  • [Remarks] 京都大学大学院医学研究科微生物感染症学

    • URL

      http://www.bac.med.kyoto-u.ac.jp

    • Related Report
      2014 Annual Research Report
  • [Remarks] 京都大学医学研究科微生物感染症学

    • Related Report
      2013 Research-status Report
  • [Remarks] 京都大学大学院医学研究科微生物感染症学

    • URL

      http://bisei15.mb.med.kyoto-u.ac.jp/index.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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