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The growth-down of Mycobacterium tuberculosis by macrophages-derived extracellular vesicles

Research Project

Project/Area Number 17K08836
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Oka Mayuko  京都府立大学, 生命環境科学研究科, 准教授 (40347498)

Co-Investigator(Kenkyū-buntansha) 堀口 安彦  大阪大学, 微生物病研究所, 教授 (00183939)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords結核菌 / マクロファージ / HIF-1alpha / 細胞外小胞 / Mycobaceria / Macrophages / Exosomes / エキソソーム / 休眠 / 休眠菌
Outline of Final Research Achievements

Macrophages are major components of tuberculosis granulomas and are responsible for host defenses against the intracellular pathogen, Mycobacterium tuberculosis (Mtb). We herein showed the strong expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in tuberculosis granulomas and in Mtb-infected mouse bone marrow-derived macrophages (BMDM). Moreover, HIF-1alpha has a role in a fundamental host-protective mechanism against Mtb. Macrophages are known to produced and secrete exosomes, extracellular vesicles, which are a key factor of inflammation. When both growth phase and latent bacilli were infected in mouse BMDM, both macrophage-derived exosomes enhanced the increase in the pro-inflammatory cytokines. However, the exosomes that were derived from HIF-1 alpha deficient macrophages, did not increase in the level of cytokines. Thus, these result suggest that HIF-1 has a role in the function of exosomes.

Academic Significance and Societal Importance of the Research Achievements

結核は、単一病原体による最大級の感染症である。ワクチンや治療薬が開発されているにもかかわらず、年間1000万人が発症するのには、休眠期結核菌が持続潜伏感染する無症候状態の患者(潜在性結核)の存在が大きい。そのため、結核菌の増殖と休眠の調節機構の解明は重要である。申請者は、肺結核肉芽腫のマクロファージに発現するHIF-1alphaが増殖期と休眠期の結核菌感染により、さらにこのHIF-1alphaが結核菌の増殖調節や細胞外小胞による炎症性サイトカイン産生に寄与することを明らかにした。HIF-1alphaがマクロファージ内での結核菌に大きな影響を与える新たな因子の1つであることを示す。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Effects of orally active hypoxia inducible factor alpha prolyl hydroxylase inhibitor, FG4592 on renal fibrogenic potential in mouse unilateral ureteral obstruction model2020

    • Author(s)
      Kabei Kazuya、Tateishi Yu、Shiota Masayuki、Osada-Oka Mayuko、Nishide Shunji、Uchida Junji、Nakatani Tatsuya、Matsunaga Shinji、Yamaguchi Takehiro、Tomita Shuhei、Miura Katsuyuki
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 142 Issue: 3 Pages: 93-100

    • DOI

      10.1016/j.jphs.2019.12.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bordet‐Gengou agar medium supplemented with albumin‐containing biologics for cultivation of bordetellae2019

    • Author(s)
      Hiramatsu Yukihiro、Osada‐Oka Mayuko、Horiguchi Yasuhiko
    • Journal Title

      Microbiology and Immunology

      Volume: 63 Issue: 12 Pages: 513-516

    • DOI

      10.1111/1348-0421.12742

    • NAID

      40022103554

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolic adaptation to glycolysis is a basic defense mechanism of macrophages for Mycobacterium tuberculosis infection2019

    • Author(s)
      Osada-Oka Mayuko、Goda Nobuhito、Saiga Hiroyuki、Yamamoto Masahiro、Takeda Kiyoshi、Ozeki Yuriko、Yamaguchi Takehiro、Soga Tomoyoshi、Tateishi Yu、Miura Katsuyuki、Okuzaki Daisuke、Kobayashi Kazuo、Matsumoto Sohkichi
    • Journal Title

      International Immunology

      Volume: 31 Issue: 12 Pages: 781-793

    • DOI

      10.1093/intimm/dxz048

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] D4+ T Responses Other Than Th1 Type Are Preferentially Induced by Latency-Associated Antigens in the State of Latent Mycobacterium tuberculosis Infection.2019

    • Author(s)
      Yamashita Y, Oe T, Kawakami K, Osada-Oka M, Ozeki Y, Terahara K, Yasuda I, Edwards T, Tanaka T, Tsunetsugu-Yokota Y, Matsumoto S, Ariyoshi K.
    • Journal Title

      Front Immunol.

      Volume: 10 Pages: 2807-2807

    • DOI

      10.3389/fimmu.2019.02807

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum antibody profiles in individuals with latent Mycobacterium tuberculosis infection2019

    • Author(s)
      Maekura Ryoji、Kitada Seigo、Osada‐Oka Mayuko、Tateishi Yoshitaka、Ozeki Yuriko、Fujicawa Takeya、Miki Mari、Jyunnko Ogawa、Mori Masahide、Matsumoto Sohkichi
    • Journal Title

      Microbiology and Immunology

      Volume: 63 Issue: 3-4 Pages: 130-138

    • DOI

      10.1111/1348-0421.12674

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-density lipoprotein suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages.2018

    • Author(s)
      Inoue M, Niki M, Ozeki Y, Nagi S, Chadeka EA, Yamaguchi T, Osada-Oka M, Ono K, Oda T, Mwende F, Kaneko Y, Matsumoto M, Kaneko S, Ichinose Y, Njenga SM, Hamano S, Matsumoto S.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 6736-6736

    • DOI

      10.1038/s41598-018-24233-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Metabolic adaptation to glycolysis is a basic defense mechanism of macrophages for M. tuberculosis2020

    • Author(s)
      Mayuko Osada-Oka, Yuriko Ozeki, Takahiro Yamaguchi, Sohkichi Matsumoto
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Metabolic Adaptation to Glycolysis by HIF-1 Is a Basic Defense Mechanism of Macrophages for Mycobacterium tuberculosis Infection2020

    • Author(s)
      Mayuko Osada-Oka, Yuriko Ozeki, Sohkichi Matsumoto
    • Organizer
      The 54th Mycobacteria Panel Meeting, US-Japan Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 大腸菌とマクロファージの細胞外小胞による異種細胞間相互作用と炎症機構2020

    • Author(s)
      岡 真優子
    • Organizer
      農芸化学会2020年度大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 結核菌の増殖を制限するマクロファージの戦略ー糖代謝酵素と転写因子HIF-1ー2019

    • Author(s)
      岡 真優子,松本壮吉
    • Organizer
      第13回細菌学若手コロッセウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] マクロファージのエキソソームを介した大腸菌感染によるNO産生機構2019

    • Author(s)
      岡 真優子,今宮里沙,小林慧子,堀口安彦,市川 寛,南山幸子
    • Organizer
      第72回日本酸化ストレス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 大腸菌外膜由来細胞外小胞によるエキソソームを介した炎症因子誘導作用2018

    • Author(s)
      岡 真優子, 今宮 里沙, 矢倉 大介, 木村 唯, 堀口 安彦, 市川 寛, 南山 幸子
    • Organizer
      第71回日本酸化ストレス学会 第18回日本NO学会 合同学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 大腸菌タンパク質によるエキソソームを介した炎症因子誘導作用2018

    • Author(s)
      今宮 里沙, 岡 真優子, 矢倉 大介, 堀口 安彦, 市川 寛, 南山 幸子
    • Organizer
      第71回日本酸化ストレス学会 第18回日本NO学会 合同学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 細菌と宿主細胞の異種細胞間での細胞外小胞を介した相互作用と炎症機構2018

    • Author(s)
      岡 真優子
    • Organizer
      第12回腸内細菌をターゲットとした食品開発研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] The role of HIF-1α-regulated genes in Mycobacterium tuberculosis-infected macrophages2018

    • Author(s)
      Mayuko Osada-Oka, Mutsumi Sato, Yuriko Ozeki, Sohkichi Matsumoto
    • Organizer
      The U.S.-Japan Cooperative Medical Sciences Program, 52nd Mycobacteria Panel Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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