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• W3201259172 abstract "Abstract Background: Thrombocytopenia is frequent in uncomplicated Plasmodium vivax malaria. Contribution of platelets to pathogenesis is unknown and poorly understood. Our study explores the platelet proteome from uncomplicated P. vivax malaria patients to fingerprint molecular pathways in relation to platelet function. Also, plasma levels of platelet activation (Platelet factor 4 – PF4/CXCL4) and endothelial activation (Von Willebrand factor – VWf) markers, in conjunction with some in vitro interactions between platelets and P. vivax infected erythrocytes ( Pv -IEs) were measured to explore platelet responses during infection and their effect on parasite development. Methods: This study was performed in a cohort of 48 patients and 25 healthy controls. Platelets were purified from a subgroup of 5 patients and 5 healthy controls to be analyzed by LC-MS/MS. In all participants enrolled in this study, PF4/CXCL4 and VWf plasma levels were measured. Finally, a subsample of 10 P. vivax isolates were co-cultured with platelets to measure P v- IE schizonts inhibition as well as platelet activation due to their interaction. Results: In total 28 out of 215 proteins were significantly abundant in the proteomes from patients. The most significantly decreased protein was PF4/CXCL4 followed by other proteins related to platelet activation, cytoskeletal remodeling, and adhesion to endothelial cells. In contrast, acute phase proteins including SERPINs and Amyloid Serum A 1 (SAA1) were increased. High VWf plasma levels in patients suggested endothelial activation. Interestingly, PF4/CXCL4 plasma levels were similar between patients and controls, but high levels of this protein were found in co-cultures, and platelets inhibited Pv -IEs development to schizonts. Conclusions: Platelet proteome from patients with uncomplicated P. vivax malaria suggests platelet degranulation, platelet activation, cytoskeletal remodeling, and adhesion to endothelial cells. According to the evidenced endothelial activation our study plus the suggested specific localization of PF4/CXCL4 during P. vivax infection due to the normal levels in plasma, and the inhibition of Pv -IE schizonts development; our study suggest that platelets are active players during the response to P . vi vax infection. Future studies are needed to further investigate the molecular pathways of interaction between altered platelet proteins and host response; which could affect parasite control as well as disease progression." @default.
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• W3201259172 date "2021-01-13" @default.
• W3201259172 modified "2023-09-27" @default.
• W3201259172 title "Uncomplicated Plasmodium vivax malaria: Mapping the proteome from circulating platelets" @default.
• W3201259172 doi "https://doi.org/10.21203/rs.3.rs-126230/v1" @default.
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