Li Xiaofeng, Wei Xuan, Deng Jiehua, Wu Xin, Feng Xin, Tang Shudan, Zhang Hui, Zhang Jianquan
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
Department of Respiratory and Critical Care Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518033, China.
Microb Pathog. 2025 Oct;207:107853. doi: 10.1016/j.micpath.2025.107853. Epub 2025 Jun 28.
In chronic obstructive pulmonary disease (COPD) patients, Candida colonization in the lower respiratory tract is associated with long-term prognosis and acute exacerbations, though the underlying mechanisms remain unclear. This study explores the impact of Candida.albicans (C.albicans) airway colonization on macrophages and airway inflammation in mice with emphysema.
A chronic emphysema mouse model was established using cigarette smoke and porcine pancreatic elastase(PPE) exposure. Mice were then instilled with C. albicans spore suspension (5 × 10 CFU/mouse) to induce airway colonization. The fungal burden in lung homogenates and the body weight change of mice were measured at 24h, 72h, and 120h post installation. At 72h, the fungal load, alveolar macrophages(AMs) polarization, reactive oxygen species(ROS) content, and NLRP3 and IL-1β expression in the airways or lungs were assessed. In vitro, THP-1-derived macrophages were treated with cigarette smoke extract (CSE), with or without antioxidant inhibitor NAC or NLRP3 inhibitor MCC950 pretreatment, followed by the stimulation of heat-killed C. albicans (HKCA) spores. The ROS production, NLRP3, and IL-1β protein expression in cells were detected.
After instilling C. albicans into the airways, the body weight changes of the mice were less than 20 % at 24h, 72h, and 120h. Fungal spores are mainly concentrated in the airways, and no spores or hyphae were detected in the alveoli or lung interstitium. The fungal load decreased by 2.5 log units at 72h. C. albicans colonization enhanced CD86, CD206, and ROS fluorescence in alveolar macrophages, increased IL-1β levels in bronchoalveolar lavage fluid (BALF), and upregulated NLRP3 and IL-1β transcription in lung tissue. In THP-1-derived macrophages, HKCA following CSE stimulation increased CD86, CD206, ROS, NLRP3, and IL-1β levels. ROS inhibition with NAC or NLRP3 inhibition with MCC950 downregulated NLRP3 and IL-1β production.
C. albicans airway colonization promotes macrophage polarization and intensifies inflammation, especially in emphysema mice. ROS production in macrophages may activate NLRP3, leading to increased IL-1β release, which could be a potential mechanism for exacerbating inflammation.
在慢性阻塞性肺疾病（COPD）患者中，下呼吸道念珠菌定植与长期预后及急性加重相关，但其潜在机制尚不清楚。本研究探讨白色念珠菌气道定植对肺气肿小鼠巨噬细胞和气道炎症的影响。
采用香烟烟雾和猪胰弹性蛋白酶（PPE）建立慢性肺气肿小鼠模型。然后给小鼠滴注白色念珠菌孢子悬液（5×10 CFU/小鼠）以诱导气道定植。在滴注后24小时、72小时和120小时测量肺匀浆中的真菌负荷和小鼠体重变化。在72小时时，评估气道或肺中的真菌载量、肺泡巨噬细胞（AMs）极化、活性氧（ROS）含量以及NLRP3和IL-1β表达。在体外，用香烟烟雾提取物（CSE）处理THP-1来源的巨噬细胞，在有或没有抗氧化剂抑制剂NAC或NLRP3抑制剂MCC950预处理的情况下，随后用热灭活的白色念珠菌（HKCA）孢子刺激。检测细胞中的ROS产生、NLRP3和IL-1β蛋白表达。
将白色念珠菌滴注到气道后，在24小时、72小时和120小时时小鼠体重变化小于20%。真菌孢子主要集中在气道中，在肺泡或肺间质中未检测到孢子或菌丝。在72小时时真菌载量下降了2.5个对数单位。白色念珠菌定植增强了肺泡巨噬细胞中的CD86、CD206和ROS荧光，增加了支气管肺泡灌洗液（BALF）中的IL-1β水平，并上调了肺组织中NLRP3和IL-1β的转录。在THP-1来源的巨噬细胞中，CSE刺激后的HKCA增加了CD86、CD206、ROS、NLRP3和IL-1β水平。用NAC抑制ROS或用MCC950抑制NLRP3下调了NLRP3和IL-1β的产生。
白色念珠菌气道定植促进巨噬细胞极化并加剧炎症，尤其是在肺气肿小鼠中。巨噬细胞中的ROS产生可能激活NLRP3，导致IL-1β释放增加，这可能是炎症加剧的潜在机制。
