Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Center of Experimental Rheumatology, University Hospital Zurich and Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Front Immunol. 2022 Jul 28;13:908211. doi: 10.3389/fimmu.2022.908211. eCollection 2022.
To understand the pathophysiology of spondylodiscitis due to , an emerging infectious disease of the intervertebral disc (IVD) and vertebral body with a high complication rate, we combined clinical insights and experimental approaches. Clinical data and histological material of nine patients suffering from spondylodiscitis were retrospectively collected at a single center. To mirror the clinical findings experimentally, we developed a novel porcine model mimicking acute spondylodiscitis and assessed the interaction between and IVD cells within their native environment. In addition, the inflammatory features underlying this interaction were assessed in primary human IVD cells. Finally, mirroring the clinical findings, we assessed primary human neutrophils for their ability to respond to secreted inflammatory modulators of IVD cells upon the challenge. Acute spondylodiscitis in patients was characterized by tissue necrosis and neutrophil infiltration. Additionally, the presence of empty IVD cells' lacunae was observed. This was mirrored in the porcine model, where induced extensive IVD cell death, leading to empty lacunae. Concomitant engagement of the apoptotic and pyroptotic cell death pathways was observed in primary human IVD cells, resulting in cytokine release. Among the released cytokines, functionally intact neutrophil-priming as well as broad pro- and anti-inflammatory cytokines which are known for their involvement in IVD degeneration were found. In patients as well as in a novel porcine model, IVD infection caused IVD cell death, resulting in empty lacunae, which was accompanied by the release of inflammatory markers and recruitment of neutrophils. These findings offer valuable insights into the important role of inflammatory IVD cell death during spondylodiscitis and potential future therapeutic approaches.
为了了解 [病原体名称] 导致的脊椎炎的病理生理学，这是一种新兴的椎间盘（IVD）和椎体感染性疾病，具有很高的并发症发生率，我们结合了临床见解和实验方法。在一个单一中心，我们回顾性地收集了 9 名患有 [病原体名称] 脊椎炎的患者的临床数据和组织学材料。为了在实验中模拟临床发现，我们开发了一种新的猪模型，模拟急性 [病原体名称] 脊椎炎，并评估了 [病原体名称] 与 IVD 细胞在其天然环境中的相互作用。此外，还在原代人 IVD 细胞中评估了这种相互作用的炎症特征。最后，模拟临床发现，我们评估了原代人中性粒细胞对 IVD 细胞分泌的炎症调节剂的反应能力，以应对 [病原体名称] 的挑战。患者的急性 [病原体名称] 脊椎炎表现为组织坏死和中性粒细胞浸润。此外，还观察到 IVD 细胞空腔的存在。在猪模型中也观察到了同样的情况，[病原体名称] 诱导了广泛的 IVD 细胞死亡，导致空腔。在原代人 IVD 细胞中观察到凋亡和细胞焦亡途径的协同作用，导致细胞因子释放。在释放的细胞因子中，发现了功能完整的中性粒细胞启动以及广泛的促炎和抗炎细胞因子，这些细胞因子已知参与了 IVD 的退化。在患者和新型猪模型中，[病原体名称] 的 IVD 感染导致 IVD 细胞死亡，导致空腔形成，同时伴有炎症标志物的释放和中性粒细胞的募集。这些发现为脊椎炎期间炎症性 IVD 细胞死亡的重要作用以及潜在的未来治疗方法提供了有价值的见解。
