Jeznach Aldona, Sidor-Dzitkowska Karolina, Bandyszewska Magdalena, Grzanka Małgorzata, Popławski Piotr, Marszalik Anna, Domagała-Kulawik Joanna, Stachowiak Radosław, Hoser Grażyna, Skirecki Tomasz
Department of Translational Immunology and Experimental Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland.
Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Warsaw, Poland.
Emerg Microbes Infect. 2025 Dec;14(1):2492206. doi: 10.1080/22221751.2025.2492206. Epub 2025 Apr 22.
has become one of the most critical pathogens causing nosocomial pneumonia. Existing animal models of pneumonia are not relevant to the majority of critical care patients. We aimed to develop a novel model of secondary pneumonia in post-sepsis mice.
A two-hit model of sepsis induced by cecal ligation and puncture followed by pneumonia on day 5 was established. In addition, the two-hit model was established in humanized mice. A period of 2 h of mechanical ventilation followed by observation was used in additional experiments. Lung histopathology, bacterial cultures, and cellular infiltration were analysed as well as markers of the inflammasome activity and .
infection caused mortality and loss of body weight and temperature in post-sepsis mice. Increased lung bacterial burden and dissemination together with signs of enhanced inflammatory injury were observed in post-sepsis mice but not control mice that were challenged with . Post-sepsis mice were unable to mount inflammasome activation in response to secondary pneumonia to the level of control mice. Transfer of wild-type but not capsase-1 KO alveolar macrophages was able to restore the pulmonary protection against . Mechanical ventilation exacerbated the pathological response to pneumonia in post-sepsis mice but enhanced inflammasome signalling in non-sepsis mice with pneumonia.
We established a novel model of pneumonia that revealed sepsis-induced impairment of inflammasome activation in alveolar macrophages is critical for the control of secondary pneumonia.
已成为引起医院获得性肺炎的最关键病原体之一。现有的肺炎动物模型与大多数重症监护患者不相关。我们旨在建立一种脓毒症后小鼠继发性肺炎的新型模型。
建立盲肠结扎和穿刺诱导的脓毒症二次打击模型，随后在第5天诱发肺炎。此外，在人源化小鼠中建立二次打击模型。在额外的实验中，采用机械通气2小时后进行观察。分析了肺组织病理学、细菌培养、细胞浸润以及炎性小体活性标志物等。
感染导致脓毒症后小鼠死亡、体重减轻和体温下降。在脓毒症后小鼠中观察到肺细菌负荷增加和播散以及炎症损伤增强的迹象，但在用……攻击的对照小鼠中未观察到。脓毒症后小鼠对继发性肺炎的反应无法将炎性小体激活提升至对照小鼠的水平。野生型而非caspase-1基因敲除的肺泡巨噬细胞的转移能够恢复对……的肺保护作用。机械通气加剧了脓毒症后小鼠对肺炎的病理反应，但增强了非脓毒症肺炎小鼠的炎性小体信号传导。
我们建立了一种新型的……肺炎模型，该模型显示脓毒症诱导的肺泡巨噬细胞炎性小体激活受损对于控制继发性……肺炎至关重要。
