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Molecular mechanisms of bone-specific immunopathology during malaria

Research Project

Project/Area Number 16H05181
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Parasitology (including sanitary zoology)
Research InstitutionOsaka University

Principal Investigator

Cevayir Coban  大阪大学, 免疫学フロンティア研究センター, 教授 (00397712)

Research Collaborator ISHII Ken  
AKIRA Shizuo  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
KeywordsBone loss / osteoclast / osteoblast / malaria / Vitamin D / RANKL / MyD88 / Plasmodium / Malaria / bone loss / plasmodium products / tissue specificity / osteoporosis / hemozoin / Hemozoin / Bone / chronic infection / Bone homeostasis / Chronic infection / Immunology
Outline of Final Research Achievements

Malaria has deadly complications; however, the long term pathological consequences of chronic malaria infection are poorly understood. We suspected that there is an association between growth retardation and malaria infection. Therefore, we investigated possible negative impact of malaria infection on bone remodeling and growth. Using mouse models mimicking chronic and self-clearing Plasmodium infection we showed that infection causes significant and long term bone loss in adult mice and growth retardation in young mice. Bone remodeling is completely suppressed during the acute phase of infection, but is highly activated immediately after the clearance of parasites, with increased osteoclastic activity skewing the balance toward bone resorption. Osteoclasts are activated by the key osteclastogenic cytokine RANKL, which was upregulated in osteoblasts through MyD88-dependent inflammation, triggered by the accumulation and long term persistence of parasite products in the bone marrow.

Academic Significance and Societal Importance of the Research Achievements

Our results highlight the risk of bone loss in malaria-infected patients. Bone loss is sustained even after recovery from malaria.Therapies promoting bone health like Vitamin D treatment coupled with anti-malarial treatment may help to improve bone health in malaria-infected individuals.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (22 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (15 results) (of which Int'l Joint Research: 8 results,  Invited: 12 results) Remarks (1 results)

  • [Journal Article] Rapid quantification of NETs in vitro and in whole blood samples by imaging flow cytometry2019

    • Author(s)
      Lelliott PM, Momota M, Lee MSJ, Kuroda E, Iijima N, Ishii KJ, Coban C.
    • Journal Title

      Cytometry A

      Volume: .. Issue: 5 Pages: 565-578

    • DOI

      10.1002/cyto.a.23767

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Does it take three to tango? An unsuspected multimorbidity of CD8+ T cell lymphoproliferative disorder, malaria, and EBV infection.2018

    • Author(s)
      Ekemen S, Uzay A, Bassullu N, Dikicioglu-Cetin E, Matsuda K, Ince U, Coban C.
    • Journal Title

      Malar Journal

      Volume: 17 (1) Issue: 1 Pages: 349-349

    • DOI

      10.1186/s12936-018-2497-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tissue-specific immunopathology during malaria infection2018

    • Author(s)
      Coban C, Lee MSJ, Ishii KJ
    • Journal Title

      Nature Reviews Immunology

      Volume: 18(4) Issue: 4 Pages: 266-278

    • DOI

      10.1038/nri.2017.138

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Unforeseen pathologies caused by malaria2017

    • Author(s)
      Lee MSJ, Coban C
    • Journal Title

      International Immunology

      Volume: 30 Issue: 3 Pages: 121-121

    • DOI

      10.1093/intimm/dxx076

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A distinct subpopulation of CD25- T-follicular regulatory cells localizes in the germinal centers2017

    • Author(s)
      James Badger Wing, Yohko Kitagawa, Michela Locci, Hannah Hume, Christopher Tay, Takayoshi Morita, Yujiro Kidani, Kyoko Matsuda, Takeshi Inoue, Tomohiro Kurosaki, Shane Crotty, Cevayir Coban, Naganari Ohkura, and Shimon Sakaguchi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 114 Issue: 31 Pages: 6400-6400

    • DOI

      10.1073/pnas.1705551114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmodium products persist in the bone marrow and promote chronic bone loss2017

    • Author(s)
      Lee MSJ, Maruyama K, Fujita Y, Konishi A, Lelliott PM, Itagaki S, Horii T, Lin JW, Khan SM, Kuroda E, Akira S, Ishii KJ, Coban C.
    • Journal Title

      Science Immunology

      Volume: 2 Issue: 12 Pages: 2-2

    • DOI

      10.1126/sciimmunol.aam8093

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Immunology of Malaria2018

    • Author(s)
      Coban C
    • Organizer
      XXXVIII. Turkish Microbiology Congress 2018, Antalay, TURKEY
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Immunology of host-Plasmodium interactions.2018

    • Author(s)
      Coban C
    • Organizer
      The 20th JSI Summer School
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Learning from mouse models: How to understand and treat tissue specific immunopathology during malaria infection?2018

    • Author(s)
      Coban C
    • Organizer
      ICOPA 2018, 14th International Congress of Parasitology Meeting, Daegu, S. KOREA
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Malaria and Vitamin D.2018

    • Author(s)
      Coban C
    • Organizer
      The 4th Japanese Society of Osteoimmunology Meeting, Okinawa, JAPAN
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Host-Plasmodium interactions at tissue level.2018

    • Author(s)
      Coban C
    • Organizer
      Immunology at the Forefront, the 9th International Symposium of IFReC
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] New insights into the interactions between malaria parasites and the host innate immune response.2018

    • Author(s)
      Coban C.
    • Organizer
      EMBO Workshop, Modelling infectious diseases in the cell and host.
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Plasmodium Infection Modulates Bone Homeostasis2017

    • Author(s)
      Lee MSJ
    • Organizer
      The 6th NIF Winter School on Advanced Immunology
    • Place of Presentation
      Singapore
    • Year and Date
      2017-01-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Host-Plasmodium interactions at tissue level.2017

    • Author(s)
      Coban C.
    • Organizer
      13th Tsukuba Primate Center Forum, NIBIOHN at Tsukuba.
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Plasmodium products persist in the bone marrow and promote chronic bone loss.2017

    • Author(s)
      Coban C.
    • Organizer
      Malaria Gordon Research Conference.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Tissue-specificity during malaria infection.2017

    • Author(s)
      Coban C.
    • Organizer
      The 13th Nagasaki-Singapore Medical Symposium / Leading Program International Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Plasmodium infection modulates bone homeostasis2016

    • Author(s)
      Lee MSJ
    • Organizer
      The 45th Annual Meeting of Japanese Society for Immunology
    • Place of Presentation
      Okinawa, JAPAN
    • Year and Date
      2016-12-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] Tissue-specific Immunopathology during Malaria2016

    • Author(s)
      Coban C
    • Organizer
      Protein Island Matsuyama (PIM) International Symposium 2016
    • Place of Presentation
      Ehime University, Matsuyama, JAPAN
    • Year and Date
      2016-09-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Malaria-induced bone disorder triggered by chronic inflammation in the bone2016

    • Author(s)
      Lee MSJ
    • Organizer
      The 16th International Congress of Immunology 2016 (ICI Melbourne)
    • Place of Presentation
      Melbourne, AUSTRALIA
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tissue-specific Immunopathology during Malaria2016

    • Author(s)
      Coban C
    • Organizer
      Molecular Immunology & Immunogenetics Congress (MIMIC-III)
    • Place of Presentation
      Antalya, TURKEY
    • Year and Date
      2016-04-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Tissue-specific Immunopathology during Malaria2016

    • Author(s)
      Coban C
    • Organizer
      . The John Curtin School of Medical Research (JCSMR)
    • Place of Presentation
      Canberra, AUSTRALIA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] http://malimm.ifrec.osaka-u.ac.jp/

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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