Abstract
BackgroundThrombocytopenia is frequent in Plasmodium vivax malaria but the role of platelets in pathogenesis is unknown. Our study explores the platelet (PLT) proteome from uncomplicated P. vivax patients, to fingerprint molecular pathways related to platelet function. Plasma levels of Platelet factor 4 (PF4/CXCL4) and Von Willebrand factor (VWf), as well as in vitro PLTs—P. vivax infected erythrocytes (Pv-IEs) interactions were also evaluated to explore the PLT response and effect on parasite development.MethodsA cohort of 48 patients and 25 healthy controls were enrolled. PLTs were purified from 5 patients and 5 healthy controls for Liquid Chromatography–Mass spectrometry (LC–MS/MS) analysis. Plasma levels of PF4/CXCL4 and VWf were measured in all participants. Additionally, P. vivax isolates (n = 10) were co-cultured with PLTs to measure PLT activation by PF4/CXCL4 and Pv-IE schizonts formation by light microscopy.ResultsThe proteome from uncomplicated P. vivax patients showed 26 out of 215 proteins significantly decreased. PF4/CXCL4 was significantly decreased followed by other proteins involved in platelet activation, cytoskeletal remodeling, and endothelial adhesion, including glycoprotein V that was significantly decreased in thrombocytopenic patients. In contrast, acute phase proteins, including SERPINs and Amyloid Serum A1 were increased. High levels of VWf in plasma from patients suggested endothelial activation while PF4/CXCL4 plasma levels were similar between patients and controls. Interestingly, high levels of PF4/CXCL4 were released from PLTs—Pv-IEs co-cultures while Pv-IEs schizont formation was inhibited.ConclusionsThe PLT proteome analyzed in this study suggests that PLTs actively respond to P. vivax infection. Altogether, our findings suggest important roles of PF4/CXCL4 during uncomplicated P. vivax infection through a possible intracellular localization. Our study shows that platelets are active responders to P. vivax infection, inhibiting intraerythrocytic parasite development. Future studies are needed to further investigate the molecular pathways of interaction between platelet proteins found in this study and host response, which could affect parasite control as well as disease progression.
Highlights
Thrombocytopenia is frequent in Plasmodium vivax malaria but the role of platelets in pathogenesis is unknown
Our study shows that platelets are active responders to P. vivax infection, inhibiting intraeryth‐ rocytic parasite development
All patients were diagnosed with P. vivax mono-infection by nested polymerase chain reaction (PCR) and classified with uncomplicated P. vivax malaria as presented the following common symptoms: headache (79%), chills (79%), sweating (76%), adynamia (71%), myalgia (61%), arthralgia (58%), anorexia (58%), sickness (50%), low back pain (34%) and vomiting (32%).Twenty-six out of 48 (54.2%) patients were male
Summary
Thrombocytopenia is frequent in Plasmodium vivax malaria but the role of platelets in pathogenesis is unknown. Our study explores the platelet (PLT) proteome from uncomplicated P. vivax patients, to fingerprint molecu‐ lar pathways related to platelet function. South America, and Colombia, are considered low endemic malaria regions where P. vivax accounts for ~ 50% of malaria cases [2]. Thrombocytopenia defined as a reduced blood platelet (PLT) count, is frequent in malaria cases, and it has been described in ~ 49% of P. vivax malaria patients in Colombia [5]. Despite the high frequency of thrombocytopenia, neither the role of PLTs in P. vivax malaria pathogenesis nor the consequences of interactions between platelets and P. vivax infected erythrocytes (Pv-IEs) are understood
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