Han Xiaoxiao, Yang Xin, Yang Xingjing, Liu Tingting, He Wenjun
School of Bioscience and Technology, Chengdu Medical College, Chengdu 610500, China.
Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases of Sichuan Higher Education Institutes, Chengdu 610500, China.
Biology (Basel). 2025 Aug 14;14(8):1049. doi: 10.3390/biology14081049.
IBV is a key pathogenic agent in poultry, causing significant respiratory and renal diseases. This study investigated NLRP3 inflammasome and pyroptosis involvement in IBV-infected chicken macrophage HD11 cells. IBV infection triggered a time-dependent increase in the release of IL-1β/IL-18, along with the upregulation of inflammasome-related genes. MCC950 treatment, an NLRP3 inhibitor, notably decreased inflammatory markers while enhancing viral replication, highlighting the NLRP3 inflammasome's function in restricting viral proliferation and mediating immunopathology. Experiments with UV-inactivated IBV demonstrated that active viral replication was essential for inflammasome activation. Pyroptosis was confirmed in IBV-infected HD11 cells through increased LDH release, characteristic ultrastructural damage, and upregulation of pyroptosis-related genes. Additionally, transfection with the IBV nucleocapsid (N) gene alone induced inflammasome activation and pyroptosis, indicating that the N protein is a key viral factor in this process. Our study offers a new understanding of IBV pathogenesis mechanisms and indicates that targeting the NLRP3 inflammasome may serve as a therapeutic approach.
传染性支气管炎病毒（IBV）是家禽中的一种关键致病因子，可引发严重的呼吸道和肾脏疾病。本研究调查了NLRP3炎性小体和细胞焦亡在IBV感染的鸡巨噬细胞HD11细胞中的作用。IBV感染引发了IL-1β/IL-18释放的时间依赖性增加，同时炎性小体相关基因上调。NLRP3抑制剂MCC950处理显著降低了炎症标志物，同时增强了病毒复制，突出了NLRP3炎性小体在限制病毒增殖和介导免疫病理学方面的作用。用紫外线灭活的IBV进行的实验表明，活跃的病毒复制对于炎性小体激活至关重要。通过增加乳酸脱氢酶（LDH）释放、典型的超微结构损伤以及细胞焦亡相关基因的上调，在IBV感染的HD11细胞中证实了细胞焦亡。此外，单独转染IBV核衣壳（N）基因可诱导炎性小体激活和细胞焦亡，表明N蛋白是这一过程中的关键病毒因子。我们的研究为IBV发病机制提供了新的认识，并表明靶向NLRP3炎性小体可能是一种治疗方法。
