A novel murine model of infective endocarditis mimics human pathophysiology

Abstract

Incidence of Infective endocarditis (IE) and its mortality rate despite optimal medical therapy remain high. Early diagnosis and treatment initiation are challenging because the involved immunological processes are poorly understood due to a lack of suitable in vivo models and their difference to human pathophysiology. Objectives: To establish a novel reproducible murine IE model, based on wire injury (WI) induced endothelial damage. Methods: IE was established by inducing endothelial damage via wire injury followed by bacterial challenge with S. aureus using 10^4–6 colony-forming units (CFU). Cross-sections of valvular leaflets were prepared for scanning electron microscopy (SEM) and immunofluorescence microscopy to visualize valvular invasion of macrophages, neutrophils, and S. aureus. Bacterial cultivation was carried out from blood and valve samples. Results: Wire injury induced endothelial damage was observed in all mice after wire-injury in SEM imaging. We reliably induced IE using 10⁵ (85%) and 10⁶ (91%) CFU S. aureus after wire injury. We found significant neutrophilia in the blood and increased valvular immune cell and bacterial accumulations in IE mice. Conclusion: Our model allows for reliable IE induction and analysis of bacterial vegetation and immune cell infiltration in vivo and ex vivo. Valvular immune cell infiltration was similar to human pathophysiology.