Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance.
Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance.
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DOI：
10.1038/s41467-021-21814-z
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发表时间：
2021-03-19
影响因子：
16.6
通讯作者：
Vickers MA
中科院分区：
文献类型：
--
作者：
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
在镰状细胞病和疟疾中，红细胞（rbc）在脾脏中被吞噬，但介导摄取的受体配体对尚未确定。在这里，我们报道了在患病或氧化的红细胞表面表达的高甘露糖n -聚糖（Man5-9GlcNAc2）斑块，结合吞噬细胞上的甘露糖受体（CD206）来介导清除。我们发现镰状细胞病的血管外溶血与红细胞上高甘露糖聚糖水平相关。此外，恶性疟原虫感染的红细胞暴露表面甘露糖n -聚糖，与缺乏血红蛋白s的红细胞相比，镰状细胞特征受试者的红细胞表面甘露糖n -聚糖含量明显更高。这些聚糖与高分子量复合物和蛋白酶抗性相关，低分子量片段含有谱蛋白。识别表面n连接的高甘露糖聚糖作为对细胞应激的响应是镰状细胞病发病机制和镰状细胞性状对严重疟疾抗性的共同分子机制。在镰状细胞病和疟疾中，红细胞在脾脏中被吞噬。在这里，Cao等人表明，暴露在患病或氧化的红细胞表面的高甘露糖n -聚糖与宿主细胞上的甘露糖受体CD206结合，介导吞噬作用。
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. Red blood cells (RBCs) are phagocytosed in the spleen in sickle cell disease and malaria. Here, Cao et al. show that high mannose N-glycans, exposed on diseased or oxidized RBC surfaces, bind mannose receptor CD206 on host cells, mediating phagocytosis.
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影响因子：
4.6
作者：
Ch'ng JH;Moll K;Quintana Mdel P;Chan SC;Masters E;Moles E;Liu J;Eriksson AB;Wahlgren M
通讯作者：
Wahlgren M
影响因子：
2.2
作者：
Corrigan, R. A.;Rowe, J. A.
通讯作者：
Rowe, J. A.
DOI：
10.1042/bj20151227
发表时间：
2016-04-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Davies MJ
通讯作者：
Davies MJ
DOI：
10.1073/pnas.1804388115
发表时间：
2018-07-10
影响因子：
11.1
作者：
Archer, Natasha M.;Petersen, Nicole;Duraisingh, Manoj T.
通讯作者：
Duraisingh, Manoj T.
影响因子：
3.9
作者：
KAKU, H;VANDAMME, EJM;GOLDSTEIN, IJ
通讯作者：
GOLDSTEIN, IJ