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

Huan Cao, Aristotelis Antonopoulos, Sadie Henderson, Heather J.h Wassall, John Brewin, Alanna Masson, Jenna Shepherd, Gabriela Konieczny, Bhinal Patel, Maria-Louise Williams, Adam Davie, Megan Amy Forrester, Lindsay Susan Hall, Beverley Minter, Dimitris Tampakis, Michael Moss, Charlotte Lennon, Wendy Pickford, Lars Erwig, Beverley RobertsonAnne Dell, Gordon Brown, Heather Wilson, David C. Rees, Stuart M Haslam, J. Alexandra Rowe, Robert Barker, Mark Vickers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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
Original languageEnglish
Article number1792
Number of pages13
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 19 Mar 2021

Keywords

  • Glycobiology
  • Malaria
  • Pattern recognition receptors
  • sickle cell disease

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