Zhu Meijun, Lu Yan, Wei Yan, Hong Fei, Ji Juhua, Song Lei
Department of Pediatrics, Nantong First People's Hospital (Affiliated Hospital 2 of Nantong University, Nantong Clinical Medical College of Kangda College of Nanjing Medical University), Nantong, Jiangsu, 226014, China.
Department of Pediatrics, Nantong First People's Hospital (Affiliated Hospital 2 of Nantong University, Nantong Clinical Medical College of Kangda College of Nanjing Medical University), Nantong, Jiangsu, 226014, China.
Cytokine. 2025 Nov;195:157014. doi: 10.1016/j.cyto.2025.157014. Epub 2025 Aug 26.
The increase in the number of macrolide-resistant Mycoplasma pneumoniae (MP) poses a threat to human health worldwide. The present research investigates the role of the NLRP3 inflammasome in mycoplasma pneumoniae pneumonia (MPP). MPP patient (n = 40) and healthy control (n = 20)-derived serum samples were collected. MP (strain ATCC15531)-infected C57BL/6 J or Nlrp3 mice with or without MCC950 treatment were used to explore the role of the NLRP3 inflammasome. The concentrations of inflammatory cytokines were determined by enzyme-linked immunosorbent assay. Histomorphological changes were determined by hematoxylin-eosin staining. The transcriptional and translational levels of NLRP3 were detected with quantitative PCR and western blot. Serum interleukin (IL)-1β and IL-18 levels were higher in MPP patients, along with elevated NLRP3 mRNA and protein levels. High NLRP3 expression was associated with fever duration, duration of admission, c-reactive protein and lactate dehydrogenase levels, and macrolide resistance. During the progression of MP infection, the NLRP3 inflammasome was progressively activated in mice, accompanied by increasing lung injury and inflammation. However, MP-infected Nlrp3 mice showed decreased lung injury and inflammation. Additionally, MCC950 weakened lung injury and inflammation in MPP mice, and the combination of azithromycin and MCC950 exerted a stronger effect than azithromycin or MCC950 alone. The NLRP3 inflammasome activation boosts lung injury, inflammation, and macrolide resistance in MPP, implying that interfering with the NLRP3 inflammasome may be a stratagem for MPP administration.
大环内酯类耐药肺炎支原体（MP）数量的增加对全球人类健康构成威胁。本研究调查了NLRP3炎性小体在支原体肺炎（MPP）中的作用。收集了MPP患者（n = 40）和健康对照者（n = 20）的血清样本。使用MP（菌株ATCC15531）感染的C57BL / 6 J或Nlrp3小鼠，无论是否接受MCC950治疗，以探讨NLRP3炎性小体的作用。通过酶联免疫吸附测定法测定炎性细胞因子的浓度。通过苏木精-伊红染色确定组织形态学变化。用定量PCR和蛋白质印迹法检测NLRP3的转录和翻译水平。MPP患者血清白细胞介素（IL）-1β和IL-18水平较高，同时NLRP3 mRNA和蛋白质水平升高。NLRP3高表达与发热持续时间、住院时间、C反应蛋白和乳酸脱氢酶水平以及大环内酯类耐药性相关。在MP感染过程中，小鼠体内的NLRP3炎性小体逐渐被激活，同时肺损伤和炎症加剧。然而，MP感染的Nlrp3小鼠肺损伤和炎症减轻。此外，MCC950减轻了MPP小鼠的肺损伤和炎症，阿奇霉素与MCC950联合使用比单独使用阿奇霉素或MCC950具有更强的效果。NLRP3炎性小体激活会加剧MPP中的肺损伤、炎症和大环内酯类耐药性，这意味着干扰NLRP3炎性小体可能是MPP治疗的一种策略。
