Macrophages conduct the dormancy of Mycobacterium tuberculosis

• Project/Area Number: 24790421
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including Mycology)
• Research Institution: Kyoto Prefectural University
• Principal Investigator: OKA Mayuko 京都府立大学, 生命環境科学研究科(系), 准教授 (40347498)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: マクロファージ / 結核 / HIF-1alpha / 糖代謝 / 低酸素

Research Abstract

For intracellular replication of Mycobacterium tuberculosis, glucose is considered one of dominant carbon sources but it is also important for energy production and maintenance cellular functions of the macrophages. However it is unknown how M. tuberculosis infection impacts on the glucose metabolism of the macrophages and in turn, how it affects on the virulence of this pathogen. Hypoxia-inducible factor-1alpha (HIF-1) is one of master regulators of glucose metabolism. In this study we examined whether that HIF-1 has some affects on intracellular growth of M. tuberculosis.
These results shows that HIF-1 protein down-regulates cellular concentration of pyruvate in the intracellular bacterial pathogen-infected macrophages via enhancing LDH-A level, and thus attenuates intracellular replication of M. tuberculosis. Our data demonstrate that regulation of glucose metabolism is critical basic mechanism in controlling intracellular pathogen.

Research Products

• [Journal Article] Biomarker for Diagnosis of Mycobacterium tuberculosis Infection (2014)
  • Author(s): Osada-Oka M, Ozeki Y, Matsumoto S, Iwao H
  • Journal Title: J The Osaka City Med Associat Volume: 61 (3. 4) Pages: 81-87
  • NAID: 40019589154
• [Journal Article] Lipid synthesis is promoted by hypoxic adipocyte-derived exosomes in 3T3-L1cells (2014)
  • Author(s): Sano S, Izumi Y, Yamaguchi T, Yamazaki T, Tanaka M, Shiota M, Osada-Oka M, Nakamura Y, Wei M, Wanibuchi H, Iwao H, Yoshiyama M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 445 Issue: 2 Pages: 327-33
  • DOI: 10.1016/j.bbrc.2014.01.183
  • Peer Reviewed
• [Journal Article] Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin G in individuals with past tuberculosis (2013)
  • Author(s): Osada-Oka M, Tateishi Y, Hirayama Y, Ozeki Y, Niki M, Kitada S, Maekura R, Tsujimura K, Koide Y, Ohara N, Yamamoto T, Kobayashi K, Matsumoto S
  • Journal Title: Microbiol Immunol Volume: 57(1) Pages: 30-7
• [Journal Article] Tolvaptan attenuates left ventricular fibrosis after acute myocardial infarction in rats (2013)
  • Author(s): Yamazaki T, Nakamura Y, Shiota M, Osada-Oka M, Fujiki H, Hanatani A, Shimada K, Miura K, Yoshiyama M, Iwao H, Izumi Y
  • Journal Title: J Pharmacol Sci Volume: 123(1) Pages: 58-66
• [Journal Article] Multicolor Flow Cytometric Analyses of CD4(+) T Cell Responses to Mycobacterium tuberculosis-Related Latent Antigens (2013)
  • Author(s): Yamashita Y, Hoshino Y, Oka M, Matsumoto S, Ariga H, Nagai H, Makino M, Ariyoshi K, Tsunetsugu-Yokota Y
  • Journal Title: Jpn J Infect Dis Volume: 66 Pages: 207-215
  • NAID: 130003381673
• [Journal Article] Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin G in individuals with past tuberculosis (2013)
  • Author(s): Osada-Oka Mayuko
  • Journal Title: Microbiology and Immunology Volume: 57 Issue: 1 Pages: 30-37
  • DOI: 10.1111/j.1348-0421.2012.12005.x
  • Peer Reviewed
• [Journal Article] Multicolor Flow Cytometric Analyses of CD4(+) T Cell Responses to Mycobacterium tuberculosis-Related Latent Antigens. (2013)
  • Author(s): Yamashita Y, Hoshino Y, Oka M, Matsumoto S, Ariga H, Nagai H, Makino M, Ariyoshi K, Tsunetsugu-Yokota Y.
  • Journal Title: Jpn J Infect Dis. Volume: 66 Pages: 207-215
  • NAID: 130003381673
  • Peer Reviewed
• [Journal Article] Tolvaptan attenuates left ventricular fibrosis after acute myocardial infarction in rats. (2013)
  • Author(s): Yamazaki T, Nakamura Y, Shiota M, Osada-Oka M, Fujiki H, Hanatani A, Shimada K, Miura K, Yoshiyama M, Iwao H, Izumi Y
  • Journal Title: J Pharmacol Sci. Volume: 20 Pages: 58-66
  • Peer Reviewed
• [Journal Article] Angiotensin AT1 receptor blockers suppress oxidized low-density lipoprotein-derived formation of foam cells (2012)
  • Author(s): Osada-Oka M, Kita H, Yagi S, Sato T, Izumi Y, Iwao H
  • Journal Title: Eur J Pharmacol Volume: 15
• [Journal Article] Red ginseng inhibits scratching behavior associated with atopic dermatitis in experimental animal models (2012)
  • Author(s): Samukawa K, Izumi Y, Shiota M, Nakao T, Osada-Oka M, Miura K, Iwao H
  • Journal Title: J Pharmacol Sci Volume: 118(3) Pages: 391-400
• [Journal Article] Tolvaptan improves left ventricular dysfunction after myocardial infarction in rats (2012)
  • Author(s): Yamazaki T, Izumi Y, Nakamura Y, Yamashita N, Fujiki H, Osada-Oka M, Shiota M, Hanatani A, Shimada K, Iwao H, Yoshiyama M
  • Journal Title: Circ Heart Fail Volume: 5(6) Pages: 794-802
• [Journal Article] Tolvaptan improves left ventricular dysfunction after myocardial infarction in rats. (2012)
  • Author(s): Yamazaki T, Izumi y Nakamura Y, Yamashita N, Fujiki H, Osada-Oka M, Shiota M, Hanatani A, Shimada K, Iwao H, Yoshiyama M.
  • Journal Title: Circ Heart Fail. Volume: 5 Issue: 6 Pages: 794-802
  • DOI: 10.1161/circheartfailure.112.968750
  • Peer Reviewed
• [Journal Article] Biomarker for diagnosis of Mycobacterium tuberculosis infection (2012)
  • Author(s): Osada-Oka M, Ozeki Y, Matsumoto S, Iwao H
  • Journal Title: The Jouenal of The Osaka City Medical Association Volume: 61 Pages: 81-87
  • NAID: 40019589154
  • Peer Reviewed
• [Journal Article] Red ginseng inhibits scratching behavior associated with atopic dermatitis in experimental animal models (2012)
  • Author(s): Samukawa K, Izumi Y, Shiota M, Nakao T, Osada-Oka M, Miura K, Iwao H
  • Journal Title: J Pharmacol Sci. Volume: 118 Pages: 391-400
  • Peer Reviewed
• [Presentation] Glycolytic enzymes and glucose concentration in macrophages regulate the replication of Mycobacteria (2014)
  • Author(s): Imagawa Y, Osada-Oka M, Ozeki Y, Matsumoto S
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 江戸川区船堀
• [Presentation] Relationship between Mycobacterium tuberculosis and protozoa infections among children in Kenya (2014)
  • Author(s): Ozeki Y, Takeda C, Okabe M, Inoue M, Oka M, Hirayama Y, Ichinose Y, Kobayashi K, Matsumoto S
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 江戸川区船堀
• [Presentation] Antigen 85A and Mycobacterial DNA-binding protein 1 are targets of IgG in individuals with past tuberculosis (2013)
  • Author(s): Osada-Oka M, Tateishi Y, Hirayama Y, Ozeki Y, Kobayashi K, Matsumoto S
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉市
• [Presentation] Rapid screening and identification of anti-mycobacterial compounds utilizing recombinant BCG (2013)
  • Author(s): Ozeki Y, Nishiuchi Y, Ogura Y, Iwamoto T, Hayashi T, Oka M, Niki M, Tateishi Y, Hirayama Y, Matsumoto S
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉市
• [Presentation] Glucose metabolism in macrophage suppresses intracellular growth of Mycobacterium tuberculosis (2013)
  • Author(s): Oka M, Matsumoto S, Kobayashi K, Nishiyama M, Shiota M, Izumi Y, Miura K, Iwao H, Minamiyama Y
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡市
• [Presentation] 結核菌感染に対するマクロファージの生体防御機構 (2013)
  • Author(s): 岡真優子、松本壮吉、尾関百合子、市川寛、南山幸子
  • Organizer: 第66回日本酸化ストレス学会
  • Place of Presentation: 名古屋市
• [Presentation] 宿主細胞内で増殖する結核菌のエネルギー産生と増殖機構 (2013)
  • Author(s): 岡真優子、松本壮吉、尾関百合子、南山幸子
  • Organizer: 第7回細菌学若手コロッセウム
  • Place of Presentation: 広島県三原市
• [Presentation] Ferritin superfamily protein-like activity in mycobacterial DNA-binding protein 1 (2013)
  • Author(s): Osada-Oka M, Matsumoto S, Ozeki Y, Minamiyama Y
  • Organizer: 6^<th> Joint Meeting of The Societies for Free Radical Research Australasia and Japan
  • Place of Presentation: in Sydney, Australia
• [Presentation] 潜在性結核のバイオマーカーとしての抗Antigen85およびMycobacterial DNA-binding protein1抗体 (2013)
  • Author(s): 岡真優子,立石善隆,平山幸雄,尾関百合子,前倉亮治,小林和夫,松本壮吉
  • Organizer: 第54回日本熱帯医学会大会
  • Place of Presentation: 長崎市
• [Presentation] Ferritin superfamily protein-like activity in mycobacterial DNA-binding protein 1 (2013)
  • Author(s): Mayuko Osada-Oka, Sohkichi Matsumoto, Yuriko Ozeki, Yukiko Minamiyama
  • Organizer: 6th Joint Meeting of The Societies for Free Radical Research Australasia and Japan
  • Place of Presentation: Sydney, Australia
• [Presentation] マクロファージの糖代謝による細胞内寄生菌の増殖作用 (2013)
  • Author(s): 岡 真優子、松本 壮吉、小林 和夫、西山 方規、塩田 正之、泉 康雄、三浦 克之、岩尾 洋、南山 幸子
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡市
• [Presentation] 潜在性結核患者の血清中での結核菌抗原に対するイムノグロブリｇ (2013)
  • Author(s): 岡 真優子、立石 善隆、平山 幸雄、尾関 百合子、小林 和夫、松本 壮吉
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉市
• [Presentation] ケニア共和国における学生の結核菌感染とhookworm感染の関連 (2013)
  • Author(s): 井上 学、岡 真優子、仁木 満美子、尾関 百合子、一瀬 休生、小林 和夫、松本 壮吉
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉市
• [Presentation] リコンビナントBCG (rBCG)を用いた迅速スクリーニング法による抗結核薬の探索と同定 (2013)
  • Author(s): 尾関 百合子、西内 由紀子、小椋 義俊、岩本 朋忠、林 哲也、岡 真優子、仁木 満美子、立石 善隆、平山 幸雄、松本 壮吉
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉市