IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-21814-z.html
   My bibliography  Save this article

Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance

Author

Listed:
  • Huan Cao

    (University of Aberdeen)

  • Aristotelis Antonopoulos

    (Imperial College London)

  • Sadie Henderson

    (Scottish National Blood Transfusion Service)

  • Heather Wassall

    (University of Aberdeen)

  • John Brewin

    (King’s College Hospital)

  • Alanna Masson

    (Aberdeen Royal Infirmary)

  • Jenna Shepherd

    (University of Aberdeen)

  • Gabriela Konieczny

    (University of Aberdeen)

  • Bhinal Patel

    (Imperial College London)

  • Maria-Louise Williams

    (University of Aberdeen)

  • Adam Davie

    (University of Aberdeen)

  • Megan A. Forrester

    (University of Aberdeen)

  • Lindsay Hall

    (University of Aberdeen)

  • Beverley Minter

    (University of Aberdeen)

  • Dimitris Tampakis

    (Loughborough University and Division of Cancer Studies, King’s College London)

  • Michael Moss

    (Scottish National Blood Transfusion Service)

  • Charlotte Lennon

    (University of Aberdeen)

  • Wendy Pickford

    (University of Aberdeen)

  • Lars Erwig

    (University of Aberdeen)

  • Beverley Robertson

    (Imperial College London)

  • Anne Dell

    (King’s College Hospital)

  • Gordon D. Brown

    (University of Aberdeen
    Medical Medical Research Council Centre for Medical Mycology at the University of Exeter)

  • Heather M. Wilson

    (University of Aberdeen)

  • David C. Rees

    (King’s College Hospital)

  • Stuart M. Haslam

    (Imperial College London)

  • J. Alexandra Rowe

    (University of Edinburgh)

  • Robert N. Barker

    (University of Aberdeen)

  • Mark A. Vickers

    (University of Aberdeen
    Scottish National Blood Transfusion Service
    Aberdeen Royal Infirmary)

Abstract

In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait.

Suggested Citation

  • Huan Cao & Aristotelis Antonopoulos & Sadie Henderson & Heather Wassall & John Brewin & Alanna Masson & Jenna Shepherd & Gabriela Konieczny & Bhinal Patel & Maria-Louise Williams & Adam Davie & Megan , 2021. "Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21814-z
    DOI: 10.1038/s41467-021-21814-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-21814-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-21814-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21814-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.