Assessment of immunosuppressive mechanism induced by Mycobacterium tuberculosis infection and development of new strategy against tuberculosis by preventing it.

• Project/Area Number: 16K08774
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Niigata University
• Principal Investigator: Ozeki Yuriko 新潟大学, 医歯学系, 助教 (00169301)
• Co-Investigator(Kenkyū-buntansha): 富山 智香子 新潟大学, 医歯学系, 准教授 (80359702)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 結核菌 / 結核菌抗原 / 制御性T細胞 / ワクチン / 制御性Ｔ細胞 / BCG / IFN-gamma / 結核

Outline of Final Research Achievements

Tuberculosis is the leading cause of death by infectious disease worldwide. Mycobacterium tuberculosis, causative agent of tuberculosis, is not eradicated from human body once infection is established. One third of world population are latently infected with Mycobacterium tuberculosis, one percent of infected population develop tuberculosis a year, however immunosuppressive disease such as HIV infection and diabetes increase the risk of development. This fact indicates that host immune system controls the development of tuberculosis. This research aims to establish new methods to control development of tuberculosis in addition to elucidate the mechanism of host immune suppression by M. tuberculosis infection. Eventually we proposed the new vaccine candidate to cancel immune suppression to host by M. tuberculosis infection.

Academic Significance and Societal Importance of the Research Achievements

結核菌は宿主の免疫防御機構を回避して排除されることなく潜伏し、宿主の弱体化に伴い発症する。この宿主免疫回避と結核発症機構については未だ解明されておらず、宿主免疫活性化によるその解除方法も確立されていない。このような背景のもと、結核は撲滅が困難な疾病のひとつとなっている。本研究では結核菌のヒト免疫抑制機構を解除して免疫活性化を誘導する方法を見いだし、新規ワクチン開発への可能性を提案した。

Research Products

• [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 Re Volume: 8 Pages: 1-11
  • DOI: 10.1038/s41598-018-24233-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya. (2017)
  • Author(s): Chadeka EA, Nagi S, Sunahara T, Cheruiyot NB, Bahati F, Ozeki Y, Inoue M, Osada-Oka M, Okabe M, Hirayama Y, Changoma M, Adachi K, Mwende F, Kikuchi M, Nakamura R, Kalenda YDJ, Kaneko S, Hirayama K, Shimada M, Ichinose Y, Njenga SM, Matsumoto S, Hamano S.
  • Journal Title: PLoS Negl Trop Dis. Volume: 11
  • DOI: 10.1371/journal.pntd.0005872
  • NAID: 120006987400
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions. (2017)
  • Author(s): Enany S, Yoshida Y, Tateishi Y, Ozeki Y, Nishiyama A, Savitskaya A, Yamaguchi T, Ohara Y, Yamamoto T, Ato M, Matsumoto S.
  • Journal Title: Scientific reports Volume: 7 Pages: 6810-6810
  • DOI: 10.1038/s41598-017-06480-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of nutritional and ambient oxygen condition on biofilm formation in Mycobacterium avium subsp. hominissuis via altered glycolipid expression (2017)
  • Author(s): Takahiro Totani, Yukiko Nishiuchi, Yoshitaka Tateishi, Yutaka Yoshida, Hiromi Kitanaka, Mamiko Niki, Yukihiro Kaneko, Sohkichi Matsumoto
  • Journal Title: Sci, Rep Volume: 7 Pages: 2045-2322
  • DOI: 10.1038/srep41775
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Pathogenic mycobacteria infect human erythrocytes in vitro. (2018)
  • Author(s): Yukiko Nishiuchi, Yoshitaka Tateishi, Yuriko Ozeki, Takehiro Yamaguchi, Sohkichi Matsumoto.
  • Organizer: 第９１回日本細菌学会総会
• [Presentation] Purification of M. tuberculosis protein, and its application for diagnosis. (2018)
  • Author(s): Yukiko Ohhara, Yuriko Ozeki, Yoshitaka Tateishi, Akihito Nishiyama, Saburo Yamamoto, Ichiro Nakagawa, Sohkichi Matsumoto.
  • Organizer: 第９１回日本細菌学会総会
• [Presentation] HDL suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophage. (2018)
  • Author(s): Yuriko Ozeki, Manabu Inoue, Mamiko Niki, Mayuko Osada-Oka, Sohkichi Matsumoto.
  • Organizer: 第９１回日本細菌学会総会
• [Presentation] A new screen for tuberculosis drug candidates utilizing a luciferase-expressing recombinant Mycobacterium bovis Bacillus Calmette-Gueren. (2018)
  • Author(s): Yuriko Ozeki, Masayuki Igarashi, Matsumi Doe, Aki Tamaru, Naoko Kinoshita, Yoshitoshi Ogura, Tomotada Iwamoto, Ryuichi Sawa, Maya Umekita, Shymma Enany, Yukiko Nishiuchi,Mayuko Osada-Oka, Tetsuya Hayashi, Mamiko Niki, Yoshitaka Tateishi, Masaki Hatano, Sohkichi Matsumoto.
  • Organizer: U.S.-Lapan Cooperative Medical Sciences Program, 52nd Mycobacteria Panel Meeting
  • Int'l Joint Research
• [Presentation] Significance of the histone-like protein with the native structure for diagnosis of asymptomatic tuberculosis (2017)
  • Author(s): Yukiko Nishida, Yuriko Ozeki, Yoshitaka Tateishi, Akihito Nishiyama, Saburo Yamamoto, Cihiro Nakayama, Sohkichi Matsumoto
  • Organizer: 第９０回 日本細菌学会総会
  • Place of Presentation: 仙台国際センター展示棟（宮城県仙台市）
  • Year and Date: 2017-03-19
• [Presentation] Histone-like protein-dependent control of mycobacterial functions critical for long-term survival (2017)
  • Author(s): Akihito Nishiyama, Shymaa Enany, Yoshitaka Tateishi, Yuriko Ozeki, Anna G Saviskaya, Takehiro Yamaguchi, Yukiko Nishida, Manabu Ato, Sohkichi Matsumoto
  • Organizer: 第９０回 日本細菌学会総会
  • Place of Presentation: 仙台国際センター展示棟（宮城県仙台市）
  • Year and Date: 2017-03-19
• [Presentation] 組換え抗酸菌による結核菌抗原のブースターワクチン抗原・診断抗原としての 有効性の検討 (2017)
  • Author(s): 尾関百合子、松本 壮吉
  • Organizer: 平成２９年度中部乳酸菌研究会総会
• [Presentation] The blockade of estrogen receptors on dendritic cells exacerbates autoimmune hepatitis. (2016)
  • Author(s): Chikako Tomiyama, Hisami Watanabe
  • Organizer: 第４５回 日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] 組換え抗酸菌による結核菌抗原の発現・精製とそのワクチン効果の検討 (2016)
  • Author(s): 尾関 百合子、 松本 壮吉
  • Organizer: 平成２８年度中部乳酸菌研究会総会
  • Place of Presentation: ヤクルト本社中央研究所（東京都国立市）、立川グランドホテル（東京都立川市）
  • Year and Date: 2016-11-18