Bisphosphoglycerate mutase deficiency protects against cerebral malaria and severe malaria-induced anemia
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24 janvier 2023
- handle: 10670/1.hsrgs7
- doi: 10.1016/j.celrep.2020.108170
Ce document est mis à disposition selon les termes de la Licence Creative Commons Attribution - Pas d’utilisation commerciale - Pas de Modification 4.0 International. / This work is licensed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License. , https://creativecommons.org/licenses/by-nc-nd/4.0/deed.fr
Mots-clés
Malaria BPGM RBC Erythropoiesis Cerebral malaria Anemia Erythrocyte metabolism Erythrocytosis Polycytemia Genetic susceptibilitySujets proches
Ague Chills and fever Intermittent fever Malarial feverCiter ce document
Guoyue Xu et al., « Bisphosphoglycerate mutase deficiency protects against cerebral malaria and severe malaria-induced anemia », Papyrus : le dépôt institutionnel de l'Université de Montréal, ID : 10.1016/j.celrep.2020.108170
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Résumé
The replication cycle and pathogenesis of the Plasmodium malarial parasite involves rapid expansion in red blood cells (RBCs), and variants of certain RBC-specific proteins protect against malaria in humans. In RBCs, bisphosphoglycerate mutase (BPGM) acts as a key allosteric regulator of hemoglobin/oxyhemoglobin. We demonstrate here that a loss-of-function mutation in the murine Bpgm (BpgmL166P) gene confers protection against both Plasmodium-induced cerebral malaria and blood-stage malaria. The malaria protection seen in BpgmL166P mutant mice is associated with reduced blood parasitemia levels, milder clinical symptoms, and increased survival. The protective effect of BpgmL166P involves a dual mechanism that enhances the host’s stress erythroid response to Plasmodium-driven RBC loss and simultaneously alters the intracellular milieu of the RBCs, including increased oxyhemoglobin and reduced energy metabolism, reducing Plasmodium maturation, and replication. Overall, our study highlights the importance of BPGM as a regulator of hemoglobin/oxyhemoglobin in malaria pathogenesis and suggests a new potential malaria therapeutic target.