Ntinopoulou Maria, Konstantinidis Theocharis, Chalkidou Anna, Papagianni Eleni, Skeva Aikaterini, Panopoulou Maria, Chrysanthopoulou Akrivi
Laboratory of Molecular Immunology, Department of Biological Applications & Technology, Faculty of Health Sciences, University of Ioannina, 45332 Ioannina, Greece.
Laboratory of Microbiology, Department of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
Int J Mol Sci. 2025 Jun 15;26(12):5733. doi: 10.3390/ijms26125733.
Hepatitis B virus (HBV) infection is one of the most dangerous viral diseases, with innate immunity representing the first line of defense against the virus. In this branch of the immune system, neutrophils are considered key cellular mediators. To better understand the implication of neutrophils in the distinct stages of the disease, HBV-infected patients were enrolled in this study and categorized into three groups: patients with acute infection, chronic infection under treatment, and at early cirrhotic stage. To elucidate the role of inflammatory mediators and cellular mechanisms of neutrophilic origin in the course of the infection, both ex vivo and in vitro studies were performed. Increased levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-18, IL-33, and citrullinated histone H3 (CitH3)-an accurate marker of neutrophil extracellular traps (NETs)-were detected in the circulation of patients with acute infection or early cirrhosis. In parallel, sera from the aforementioned patient groups induced the formation of IL-1b-bearing NETs in neutrophils from healthy individuals. These inflammatory NETs affected primary fibroblasts towards acquiring a pro-fibrotic phenotype. These results suggest that NETs could be regarded as mediators in hepatitis B manifestations, while their therapeutic targeting could enhance the management of early-stage cirrhotic patients.
乙型肝炎病毒（HBV）感染是最危险的病毒性疾病之一，固有免疫是抵御该病毒的第一道防线。在这一免疫系统分支中，中性粒细胞被视为关键的细胞介质。为了更好地理解中性粒细胞在疾病不同阶段的作用，本研究纳入了HBV感染患者，并将其分为三组：急性感染患者、接受治疗的慢性感染患者和早期肝硬化患者。为了阐明炎症介质的作用以及中性粒细胞来源的细胞机制在感染过程中的作用，进行了体外和体内研究。在急性感染或早期肝硬化患者的循环中检测到C-C基序趋化因子配体2（CCL2）、白细胞介素（IL）-18、IL-33和瓜氨酸化组蛋白H3（CitH3，中性粒细胞胞外诱捕网（NETs）的准确标志物）水平升高。同时，上述患者组的血清诱导健康个体中性粒细胞中形成含IL-1β的NETs。这些炎性NETs使原代成纤维细胞获得促纤维化表型。这些结果表明，NETs可被视为乙型肝炎表现的介质，而对其进行治疗靶向可能会改善早期肝硬化患者的治疗。
