1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Plasmodium-infected erythrocytes induce secretion of IGFBP7 to form type II rosettes and escape phagocytosis

  1. Wenn-Chyau Lee
  2. Bruce Russell
  3. Radoslaw Mikolaj Sobota
  4. Khairunnisa Ghaffar
  5. Shanshan W Howland
  6. Zi Xin Wong
  7. Alexander G Maier
  8. Dominique Dorin-Semblat
  9. Subhra Biswas
  10. Benoit Gamain
  11. Yee-Ling Lau
  12. Benoit Malleret
  13. Cindy Chu
  14. François Nosten
  15. Laurent Renia  Is a corresponding author
  1. Agency for Science, Technology and Research (A*STAR), Singapore
  2. University of Otago, New Zealand
  3. Australian National University, Australia
  4. INSERM, France
  5. University of Malaya, Malaysia
  6. Mahidol University, Thailand
Research Article
  • Cited 2
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Cite this article as: eLife 2020;9:e51546 doi: 10.7554/eLife.51546

Abstract

In malaria, rosetting is described as a phenomenon where an infected erythrocyte (IRBC) is attached to uninfected erythrocytes (URBC). In some studies, rosetting has been associated with malaria pathogenesis. Here, we have identified a new type of rosetting. Using a step-by-step approach, we identified IGFBP7, a protein secreted by monocytes in response to parasite stimulation, as a rosette-stimulator for Plasmodium falciparum- and P. vivax-IRBC. IGFBP7-mediated rosette-stimulation was rapid yet reversible. Unlike type I rosetting that involves direct interaction of rosetting ligands on IRBC and receptors on URBC, The IGFBP7-mediated, type II rosetting requires two additional serum factors, namely Von Willebrand Factor and Thrombospondin-1. These two factors interact with IGFBP7 to mediate rosette formation by the IRBC. Importantly, the IGFBP7-induced type II rosetting hampers phagocytosis of IRBC by host phagocytes.

Article and author information

Author details

  1. Wenn-Chyau Lee

    Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  2. Bruce Russell

    Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  3. Radoslaw Mikolaj Sobota

    Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  4. Khairunnisa Ghaffar

    Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  5. Shanshan W Howland

    Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  6. Zi Xin Wong

    Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  7. Alexander G Maier

    Biomedical Sciences and Biochemistry/ Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Dominique Dorin-Semblat

    Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, BIGR, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Subhra Biswas

    Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  10. Benoit Gamain

    Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, BIGR, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Yee-Ling Lau

    Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
    Competing interests
    The authors declare that no competing interests exist.
  12. Benoit Malleret

    Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  13. Cindy Chu

    Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  14. François Nosten

    Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7951-0745
  15. Laurent Renia

    Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
    For correspondence
    renia_laurent@immunol.a-star.edu.sg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0349-1557

Funding

Agency for Science, Technology and Research (SIgN core funding)

  • Wenn-Chyau Lee
  • Khairunnisa Ghaffar
  • Shanshan W Howland
  • Subhra Biswas
  • Benoit Malleret
  • Laurent Renia

Agency for Science, Technology and Research (JCO-DP BMSI/15-800006-SIGN)

  • Laurent Renia

Open Fund-Young Individual Research Grant, National Medical Research Council, Ministry of Health, Singapore (OF-YIRG NMRC/OFYIRG/0070/2018)

  • Wenn-Chyau Lee

University of Malaya High Impact Research Grant (UM.C/HIR/MOHE/MED/16)

  • Yee-Ling Lau

Agency for Science, Technology and Research (IMCB Core funding)

  • Radoslaw Mikolaj Sobota

Agency for Science, Technology and Research (Young Investigator Grant YIG 2015)

  • Radoslaw Mikolaj Sobota

Wellcome Trust (SMRU is part of the Mahidol-Oxford University Research Unit)

  • Cindy Chu
  • François Nosten

NUHS start-up funding (NUHSRO/2018/006/SU/01)

  • Benoit Malleret

NUHS seed fund (NUHRO/2018/094/T1)

  • Benoit Malleret

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Urszula Krzych, Walter Reed Army Institute of Research, United States

Publication history

  1. Received: September 2, 2019
  2. Accepted: January 27, 2020
  3. Accepted Manuscript published: February 18, 2020 (version 1)
  4. Version of Record published: February 28, 2020 (version 2)

Copyright

© 2020, Lee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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