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The molecular basis of autophagy involved in host defense against pneumococcal infection and its application to therapy

Research Project

Project/Area Number 17K10042
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionTokyo Medical University (2019)
National Institute of Infectious Diseases (2017-2018)

Principal Investigator

Nakamura Shigeki  東京医科大学, 医学部, 主任教授 (20399752)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肺炎球菌 / マクロファージ / オートファジー / CCL2 / 鼻咽頭クリアランス / 感染症 / 内科
Outline of Final Research Achievements

Pretreatment of macrophages with an autophagy inhibitor significantly reduced Ccl2 mRNA expression in the pneumococcal MOI 100-exposed group. Next, when Western blot was performed by stimulating J774 cells with Streptococcus pneumoniae, ATG5 and LC3 were detected, and the detection intensity was weakened by pretreatment with wortmannin. In fluorescent staining with anti-LC3 antibody, LC3 expression level increased by pneumococcal inoculation, and LC3 expression level decreased by wortmannin pretreatment. Observation with a transmission electron microscope confirmed the formation of a bilayer membrane structure that is considered to be an autophagosome that incorporated pneumococcal cells.
This study suggests that autophagy may be involved in the immune response to pneumococci by macrophages in terms of both phagocytosis and inflammatory response.

Academic Significance and Societal Importance of the Research Achievements

肺炎球菌感染、特に鼻咽頭クリアランスにおける宿主免疫応答が十分解明されておらず、また鼻咽頭クリアランスに着目した予防戦略もこれまでに認められていない。今回の研究成果は肺炎球菌に対するマクロファージ依存性防御機構、いわゆる自然免疫活性化による感染症防御法の新知見をオートファジーとの関連から明らかにしたものである。鼻粘膜局所におけるマクロファージのオートファジー活性化に基づくクリアランス機構の亢進による新たな肺炎球菌予防法を提案するものであり、将来的な臨床応用と社会福祉への貢献も可能であると考える。

Report

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

    (9 results)

All 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (1 results)

  • [Journal Article] Mycotic pseudoaneurysm of a pulmonary artery branch caused by Cladosporium.2018

    • Author(s)
      Sunagawa K, Uchino Y, Ishimoto S, Nakamura S, Honma T, Nakanishi Y, Hatta Y, Miyazaki Y, Sakurai H, Hao H, Sugitani M.
    • Journal Title

      Pathol Int.

      Volume: 68 Pages: 47-52

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy and Safety of Intravenous Peramivir Compared With Oseltamivir in High-Risk Patients Infected With Influenza A and B Viruses: A Multicenter Randomized Controlled Study2017

    • Author(s)
      Nakamura Shigeki、Miyazaki Taiga、Izumikawa Koichi、Kakeya Hiroshi、Saisho Yutaka、Yanagihara Katsunori、Miyazaki Yoshitsugu、Mukae Hiroshi、Kohno Shigeru
    • Journal Title

      Open Forum Infectious Diseases

      Volume: 4 Issue: 3

    • DOI

      10.1093/ofid/ofx129

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pulmonary Actinomycosis Mimicking Pulmonary Aspergilloma and a Brief Review of the Literature2017

    • Author(s)
      Higashi Yoshitsugu、Nakamura Shigeki、Ashizawa Nobuyuki、Oshima Kazuhiro、Tanaka Akitaka、Miyazaki Taiga、Izumikawa Koichi、Yanagihara Katsunori、Yamamoto Yoshihiro、Miyazaki Yoshitsugu、Mukae Hiroshi、Kohno Shigeru
    • Journal Title

      Internal Medicine

      Volume: 56 Issue: 4 Pages: 449-453

    • DOI

      10.2169/internalmedicine.56.7620

    • NAID

      130005345660

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical and microbiological characteristics of breakthrough candidemia in allogeneic hematopoietic stem cell transplant recipients in a Japanese hospital.2017

    • Author(s)
      Kimura M, Araoka H, Yamamoto H, Asano-Mori Y, Nakamura S, Yamagoe S, Ohno H, Miyazaki Y, Abe M, Yuasa M, Kaji D, Kageyama K, Nishida A, Ishiwata K, Takagi S, Yamamoto G, Uchida N, Izutsu K, Wake A, Taniguchi S, and Yoneyama A.
    • Journal Title

      Antimicrob. Agents Chemother

      Volume: 182 Issue: 4 Pages: 847-853

    • DOI

      10.1128/aac.01791-16

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparative efficacies of daptomycin, vancomycin, and linezolid in experimental enterococcal peritonitis2017

    • Author(s)
      Kajihara Toshiki、Nakamura Shigeki、Iwanaga Naoki、Oshima Kazuhiro、Hirano Katsuji、Miyazaki Taiga、Izumikawa Koichi、Yanagihara Katsunori、Miyazaki Yoshitsugu、Hattori Noboru、Kohno Nobuoki、Kohno Shigeru、Mukae Hiroshi
    • Journal Title

      J Infect Chemoth

      Volume: 23 Issue: 7 Pages: 498-501

    • DOI

      10.1016/j.jiac.2016.12.002

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species2017

    • Author(s)
      Nagayoshi Yohsuke、Miyazaki Taiga、Shimamura Shintaro、Nakayama Hironobu、Minematsu Asuka、Yamauchi Shunsuke、Takazono Takahiro、Nakamura Shigeki、Yanagihara Katsunori、Kohno Shigeru、Mukae Hiroshi、Izumikawa Koichi
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 7 Pages: e0180990-e0180990

    • DOI

      10.1371/journal.pone.0180990

    • NAID

      120006987443

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case series of histoplasmosis patients with elevated serum soluble interleukin-2 receptor levels2017

    • Author(s)
      Hirayama T, Takazono T, Iwata K, Senju H, Shimazaki T, Tashiro M, Saijo T, Tanaka T, Nakamura S, Imamura Y, Kojiro M, Miyazaki T, Tsukamoto M, Furumoto A, Morimoto K, Muraosa Y, Matsubara Y, Yanagihara K, Mukae H, Kamei K, Kohno S, Izumikawa K
    • Journal Title

      J Infect Chemother.

      Volume: 23 Issue: 9 Pages: 642-647

    • DOI

      10.1016/j.jiac.2017.03.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro and In vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gatiii: an emerging fungal pathogen.2017

    • Author(s)
      Nishikawa H, Fukuda Y, Mitsuyama J, Tashiro M, Tanaka A, Takazono T, Saijo T, Yamamoto K, Nakamura S, Imamura Y, Miyazaki T, Kakeya H, Yamamoto Y, Yanagihara K, Mukae H, Kohno S, Izumikawa K.
    • Journal Title

      Journal of Antimicrobial Chemotherapy

      Volume: 72 Issue: 6 Pages: 1709-1713

    • DOI

      10.1093/jac/dkx020

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 肺炎球菌に対する宿主免疫2018

    • Author(s)
      中村茂樹
    • Organizer
      第91回日本細菌学会ワークショップ11
    • Related Report
      2018 Research-status Report

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

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