Bartsch Benedikt, Ackerschott Ansgar, Al Zaidi Muntadher, Jamin Raul Nicolas, Nazir Mariam Louis Fathy, Altrogge Moritz, Fester Lars, Lambertz Jessica, Coburn Mark, Nickenig Georg, Parcina Marijo, Zimmer Sebastian, Weisheit Christina Katharina
Department of Internal Medicine-II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany.
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
PLoS One. 2025 Apr 7;20(4):e0318955. doi: 10.1371/journal.pone.0318955. eCollection 2025.
Infective endocarditis (IE) is frequently caused by Staphylococcus aureus (S. aureus) and most commonly affects the aortic valve. Early diagnosis and treatment initiation are challenging because the involved immunological processes are poorly understood due to a lack of suitable in vivo models.
To establish a novel reproducible murine IE model, based on ultrasound-guided wire injury (WI) induced endothelial damage.
IE was established by inducing endothelial damage via ultrasound-guided wire injury followed by bacterial challenge with S. aureus using 104-6 colony-forming units (CFU) 24h to 72h after wire injury. 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. Systemic immune response was assessed using flow cytometry.
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. Aortic regurgitation was more prevalent in wire injury mice after bacterial challenge. Mice undergoing bacterial challenge responded with significant neutrophilia and elevated pro-inflammatory cytokines in the blood. Immunofluorescence staining revealed significantly increased immune cell accumulations using our proposed model compared to controls.
Echocardiography and ex vivo histological staining demonstrated consistent infective endocarditis induction in our new model, combining a wire injury-induced endothelial damage and S. aureus administration. Further exploration of the initial immune cell response and biomarker expression could potentially identify indicators for early IE diagnosis and novel treatment targets.
感染性心内膜炎（IE）常由金黄色葡萄球菌（S. aureus）引起，最常累及主动脉瓣。由于缺乏合适的体内模型，对相关免疫过程了解不足，早期诊断和开始治疗具有挑战性。
基于超声引导钢丝损伤（WI）诱导的内皮损伤，建立一种新型可重复的小鼠IE模型。
通过超声引导钢丝损伤诱导内皮损伤，然后在钢丝损伤后24至72小时用104 - 6集落形成单位（CFU）的金黄色葡萄球菌进行细菌攻击来建立IE模型。制备瓣膜小叶的横截面用于扫描电子显微镜（SEM）和免疫荧光显微镜检查，以观察巨噬细胞、中性粒细胞和金黄色葡萄球菌对瓣膜的侵袭。从血液和瓣膜样本中进行细菌培养。使用流式细胞术评估全身免疫反应。
在SEM成像中，所有钢丝损伤后的小鼠均观察到钢丝损伤诱导的内皮损伤。钢丝损伤后，我们使用105（85%）和106（91%）CFU的金黄色葡萄球菌可靠地诱导了IE。细菌攻击后，钢丝损伤小鼠中主动脉反流更为普遍。接受细菌攻击的小鼠血液中出现明显的中性粒细胞增多和促炎细胞因子升高。与对照组相比，使用我们提出的模型免疫荧光染色显示免疫细胞积累明显增加。
超声心动图和离体组织学染色表明，在我们的新模型中，结合钢丝损伤诱导的内皮损伤和金黄色葡萄球菌给药，可一致诱导感染性心内膜炎。对初始免疫细胞反应和生物标志物表达的进一步探索可能会确定早期IE诊断指标和新的治疗靶点。
