Scientists have identified specific sugars that are created on red blood cells in both malaria and sickle cell disease, helping to pinpoint the link between the two diseases.
Sickle cell disease has been linked to red blood cell changes that also offer protection against severe malaria. However, the mechanism underlying this protection has not been fully explained.
A team jointly led by Professors Robert Barker and Mark Vickers of the University of Aberdeen searched for signs appearing on red blood cells in both sickle cell disease and malaria, which highlight them for destruction in the spleen by the white blood cells called phagocytes.
The team found that patches of mannose sugars develop on the cell surfaces due to oxidative stress and bind to the mannose receptor on phagocytes. The process by which phagocytes recognise surface mannose sugars is "common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait", they report.
These sugars "act as damage-associated and pathogen-associated molecular patterns and are important in mediating both beneficial and pathological effects of sickle cell", they explain.
Professor Vickers said: “Malaria and sickle cell disease are responsible for hundreds of thousands of deaths a year but many aspects of how the body's immune system reacts to these diseases are not fully understood.
“This collaborative project has revealed more than ever before about the chains of events that occur in these diseases and can hopefully contribute to research into new treatments."
Co-author Professor Gordon Brown from the University of Exeter added: “This is a truly seminal discovery with exciting implications for future therapeutic approaches to treat a range of diseases including malaria and sickle cell disease.”
Cao H, Antonopoulos A, Henderson S, Wassall H, Brewin J, Masson A, Shepherd J, Konieczny G, Patel B, Williams ML, Davie A, Forrester MA, Hall L, Minter B, Tampakis D, Moss M, Lennon C, Pickford W, Erwig L, Robertson B, Dell A, Brown GD, Wilson HM, Rees DC, Haslam SM, Alexandra Rowe J, Barker RN, Vickers MA. (2021) “Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance.” Nature Communications doi: 10.1038/s41467-021-21814-z
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