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

Huan Cao, Aristotelis Antonopoulos, Sadie Henderson, Heather Wassall, John Brewin, Alanna Masson, Jenna Shepherd, Gabriela Konieczny, Bhinal Patel, Maria-Louise Williams, Adam Davie, Megan A. Forrester, Lindsay Hall, Beverley Minter, Dimitris Tampakis, Michael Moss, Charlotte Lennon, Wendy Pickford, Lars Erwig, Beverley Robertson, Anne Dell, Gordon D. Brown, Heather M. Wilson, David C. Rees, Stuart M. Haslam, J. Alexandra Rowe (), Robert N. Barker and Mark A. Vickers ()
Additional contact information
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
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

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21814-z

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DOI: 10.1038/s41467-021-21814-z

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