Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Cell Death Dis. 2024 Jul 31;15(7):548. doi: 10.1038/s41419-024-06892-3.
Tuberculosis (TB) remains one of the top 10 causes of death worldwide and still poses a serious challenge to public health. Recent attention to neutrophils has uncovered unexplored areas demanding further investigation. Therefore, the aim of this study was to determine neutrophil activation and circulatory neutrophil extracellular trap (NET) formation in various types of TB. Sera from TB patients (n = 91) and healthy controls (NHD; n = 38) were analyzed for NE-DNA and MPO-DNA complexes, cell-free DNA (cfDNA), and protease activity (elastase). We show that these NET parameters were increased in TB sera. Importantly, NET formation and NE activity were elevated in TB patients with extensive tissue damage when compared to those with minor damage and in patients with relapse, compared to new cases. We discuss the importance of balancing NET formation to prevent tissue damage or even relapse and argue to analyze circulating NET parameters to monitor the risk of disease relapse. To investigate the tissues for NETs and to find the source of the circulating NET degradation products, we collected sections of granulomas in lung and lymph node biopsies. Samples from other diseases with granulomas, including sarcoidosis (SARC) and apical periodontitis (AP), served as controls. Whereas NET formation characterizes the caseating granulomas, both caseating and non-caseating granulomas harbor DNA with unusual conformation. As TB is associated with hypercoagulation and thromboembolism, we further imaged the pulmonary vessels of TB patients and detected vascular occlusions with neutrophil aggregates. This highlights the dual role of neutrophils in the pathology of TB.
结核病（TB）仍然是全球十大死因之一，仍然对公共卫生构成严重挑战。最近对中性粒细胞的关注揭示了需要进一步研究的未探索领域。因此，本研究旨在确定各种类型结核病中中性粒细胞的激活和循环中性粒细胞胞外陷阱（NET）的形成。分析了结核病患者（n=91）和健康对照者（NHD；n=38）的血清中 NE-DNA 和 MPO-DNA 复合物、无细胞 DNA（cfDNA）和蛋白酶活性（弹性蛋白酶）。我们表明，这些 NET 参数在结核病血清中增加。重要的是，与损伤较小的患者相比，与新发病例相比，广泛组织损伤的结核病患者的 NET 形成和中性粒细胞活性升高。我们讨论了平衡 NET 形成以防止组织损伤甚至复发的重要性，并主张分析循环 NET 参数以监测疾病复发的风险。为了研究 NET 的组织并找到循环 NET 降解产物的来源，我们收集了肺和淋巴结活检中肉芽肿的切片。来自其他肉芽肿疾病的样本，包括结节病（SARC）和根尖周炎（AP），作为对照。虽然 NET 形成是干酪样肉芽肿的特征，但干酪样和非干酪样肉芽肿都含有具有异常构象的 DNA。由于结核病与高凝和血栓栓塞有关，我们进一步对结核病患者的肺部血管进行成像，并检测到含有中性粒细胞聚集物的血管阻塞。这突出了中性粒细胞在结核病病理学中的双重作用。
