肺炎克雷伯菌
炎症体
菌血症
肺炎
肺
医学
骨髓
免疫学
肺炎链球菌
微生物学
炎症
生物
内科学
抗生素
大肠杆菌
基因
生物化学
作者
Femke Hollwedel,Regina Maus,Jennifer Stolper,Danny Jonigk,Christina B. Hildebrand,Tobias Welte,Christina Brandenberger,Ulrich A. Maus
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2022-10-20
卷期号:209 (11): 2172-2180
被引量:2
标识
DOI:10.4049/jimmunol.2200413
摘要
The pathomechanisms underlying the frequently observed fatal outcome of Klebsiella pneumoniae pneumonia in elderly patients are understudied. In this study, we examined the early antibacterial immune response in young mice (age 2-3 mo) as compared with old mice (age 18-19 mo) postinfection with K. pneumoniae Old mice exhibited significantly higher bacterial loads in lungs and bacteremia as early as 24 h postinfection compared with young mice, with neutrophilic pleuritis nearly exclusively developing in old but not young mice. Moreover, we observed heavily increased cytokine responses in lungs and pleural spaces along with increased mortality in old mice. Mechanistically, Nlrp3 inflammasome activation and caspase-1-dependent IL-1β secretion contributed to the observed hyperinflammation, which decreased upon caspase-1 inhibitor treatment of K. pneumoniae-infected old mice. Irradiated old mice transplanted with the bone marrow of young mice did not show hyperinflammation or early bacteremia in response to K. pneumoniae Collectively, the accentuated lung pathology observed in K. pneumoniae-infected old mice appears to be due to regulatory defects of the bone marrow but not the lung, while involving dysregulated activation of the Nlrp3/caspase-1/IL-1β axis.
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