The influence of platelets and platelet-derived signalling molecules for the development of platelet-neutrophil-bacteria complexes and NETosis in the pathogenesis of infective endocarditis

• Applicant: Dr. Monika Zdanyte
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 553816927

Infective endocarditis is an acute or subacute-chronic febrile illness that rapidly damages heart valves, mural endocardium or intracardiac devices. The overall mortality from infective endocarditis ranges from 14 to 46% and remains high, despite the modern antimicrobial therapies. Infective endocarditis usually involves damaged valves. This endothelial damage leads to platelet adhesion and activation resulting in a complex interaction between platelets, bacteria, and neutrophils. Multiple layers of bacteria-platelet aggregates which adhere to the damaged endothelium form a biofilm, which results in a bacterial vegetation. Platelets also activate the coagulation cascade and stimulate neutrophil extracellular trap (NET) formation which isolates the pathogens at the sight of infection. Platelets are of crucial importance in the process of thrombo-inflammation, as they secrete various signalling molecules (e.g. HMGB-1, Cyclophilin A, Dickkopf 1), which recruit and activate immune cells at the sight of inflammation. The current research project aims to investigate the role of platelets, particularly platelet-derived signalling molecules, in the interactions between S. aureus, platelets, and neutrophils in the pathogenesis of infective endocarditis. We hypothesize that platelet-neutrophil interaction and NETosis as well as platelet-orchestrated valvular inflammation are of crucial importance for the development of infective endocarditis. In summary, this research project has the goal to elucidate these questions: 1) What is the role of particular platelet-derived signalling molecules, such as HMGB-1, Cyclophilin A, Dickkopf 1 in the pathogenesis of infective endocarditis? 2) How do platelet-derived signalling molecules, such as HMGB-1, Cyclophilin A, Dickkopf 1 modify the function of neutrophils and NETosis in the course of infective endocarditis? 3) What are possible diagnostic tools and therapeutic interventions based on the findings to improve the outcome of patients with infective endocarditis? What is the potential influence of antiplatelet therapy on endocarditis vegetation?

• DFG Programme: WBP Position