Tracking the response to Pseudomonas aeruginosa infection in ozone-induced chronic obstructive pulmonary disease mouse models.
Tracking the response to Pseudomonas aeruginosa infection in ozone-induced chronic obstructive pulmonary disease mouse models.
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DOI：
10.1016/j.biopha.2022.112980
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发表时间：
2022-04
期刊：
影响因子：
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通讯作者：
Lei Han;Yuning G. Huang;Qiang Fu;Yishu Xue;Feng-ming Ding;M. Zhang
中科院分区：
文献类型：
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作者：
Lei Han;Yuning G. Huang;Qiang Fu;Yishu Xue;Feng-ming Ding;M. Zhang
铜绿假单胞菌（P. aeruginosa）通常从COPD患者的痰中分离。然而，P.呼吸道感染在COPD进展中的作用，特别是其在改变炎症中的作用尚不清楚。本研究设计了P.动态观察肺结构、肺炎症微环境、肺功能的变化。感染后，粘液分泌水平在第3天达到峰值，并在整个研究期间保持较高水平，气道重塑和肺气肿在第14天和第21天非常明显。第3天，干扰素-γ和白细胞介素（IL）-5水平迅速升高，伴随着T-bet mRNA表达和CD 4 +T-bet+细胞的升高;（第14和21天），与GATA 3 mRNA表达增加和CD 4 + GATA 3+细胞一致，IL-4和IL-13水平显著增加; IL-17 A水平、Foxp 3 mRNA表达、CD 4 +ROR-γt+细胞和CD 4 + FOXP 3+细胞在整个感染过程中保持较高水平。小气道功能从第3天到第21天出现下降;大气道功能在第14天和第21天出现下降。总体而言，铜绿假单胞菌感染有助于COPD的进展。在感染过程中，早期Th 1相关炎症逐渐转变为晚期Th 2相关炎症，小气道功能下降早于大气道功能下降。在控制感染的基础上，适当使用糖皮质激素可通过减轻Th 2相关炎症反应的增强来延缓疾病进展，小气道也可作为P的重要治疗靶点。呼吸道感染的COPD患者。
Pseudomonas aeruginosa (P. aeruginosa)is commonly isolated from the sputum of COPD patients. However, the precise role ofP. aeruginosainfection in the progression of COPD, especially its role in altering inflammation remains unclear. Here, we designed mice models of COPD infected withP. aeruginosa(PA) and observed dynamic changes of lung structure, lung inflammatory microenvironment, lung function. After infection, the level of mucus secretion peaked on day 3 and remained higher throughout the study period, and the airway remodeling and emphysema was starkly apparent on day 14 and 21. On day 3, interferon-γ and interleukin (IL)− 5 levels increased rapidly, accompanied by elevated T-bet mRNA expression and CD4+T-bet+cells; at the late stage of infection (days 14 and 21), consistent with increased GATA3 mRNA expression and CD4+GATA3+cells, IL-4 and IL-13 levels significantly increased; IL-17A level, Foxp3 mRNA expression, CD4+ROR-γt+cells and CD4+FOXP3+cells remained at higher levels throughout the course of the infection. Small-airway function showed a decline from day 3 to day 21; large airway function showed a decline on day 14 and 21. Overall,P. aeruginosainfection contributed to the progression of COPD. During the infection, an early Th1-related inflammation gradually shifted to a later Th2-related inflammation, and small-airway function decline occurred earlier than that of large-airway function. On the basis of infection control, the appropriate use of glucocorticoid might slow disease progression by mitigating the enhanced Th2-related inflammation, and small airways could be also an important treatment target inP. aeruginosa-infected COPD patients.