Sickle Cell Trait Modulates the Proteome and Phosphoproteome of Plasmodium falciparum-Infected Erythrocytes

• Main Authors: Margaux Chauvet, Cerina Chhuon, Joanna Lipecka, Sébastien Dechavanne, Célia Dechavanne, Murielle Lohezic, Margherita Ortalli, Damien Pineau, Jean-Antoine Ribeil, Sandra Manceau, Caroline Le Van Kim, Adrian J. F. Luty, Florence Migot-Nabias, Slim Azouzi, Ida Chiara Guerrera, Anaïs Merckx
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-03-01
• Series: Frontiers in Cellular and Infection Microbiology
• Subjects: Plasmodium falciparum; hemoglobin S; erythrocyte; membrane phosphorylation; proteomics
• Online Access: https://www.frontiersin.org/articles/10.3389/fcimb.2021.637604/full

The high prevalence of sickle cell disease in some human populations likely results from the protection afforded against severe Plasmodium falciparum malaria and death by heterozygous carriage of HbS. P. falciparum remodels the erythrocyte membrane and skeleton, displaying parasite proteins at the erythrocyte surface that interact with key human proteins in the Ankyrin R and 4.1R complexes. Oxidative stress generated by HbS, as well as by parasite invasion, disrupts the kinase/phosphatase balance, potentially interfering with the molecular interactions between human and parasite proteins. HbS is known to be associated with abnormal membrane display of parasite antigens. Studying the proteome and the phosphoproteome of red cell membrane extracts from P. falciparum infected and non-infected erythrocytes, we show here that HbS heterozygous carriage, combined with infection, modulates the phosphorylation of erythrocyte membrane transporters and skeletal proteins as well as of parasite proteins. Our results highlight modifications of Ser-/Thr- and/or Tyr- phosphorylation in key human proteins, such as ankyrin, β-adducin, β-spectrin and Band 3, and key parasite proteins, such as RESA or MESA. Altered phosphorylation patterns could disturb the interactions within membrane protein complexes, affect nutrient uptake and the infected erythrocyte cytoadherence phenomenon, thus lessening the severity of malaria symptoms.