Gu Lingui, Zhu Jinjin, Nie Qingbing, Xie Binghua, Xue Shuo, Zhang Ailing, Li Qiangwei, Zhang Zhengzhong, Li Shupeng, Li Yusen, Shi Qinquan, Shi Weiwei, Zhao Lei, Liu Shuzhen, Shi Xuanming
The School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, 230023, P. R. China.
The Fuyang Hospital, Anhui Medical University, Fuyang, Anhui, 236000, P. R. China.
Commun Biol. 2025 Jan 7;8(1):20. doi: 10.1038/s42003-025-07462-9.
Gram-positive bacterial pneumonia is a significant cause of hospitalization and death. Shortage of a good experimental model and therapeutic targets hinders the cure of acute lung injury (ALI). This study has established a mouse model of ALI using Gram-positive bacteria Lactobacillus casie cell wall extracts (LCWE) and identified the key regulator NLRP3. We show that LCWE induces TNF, NF-κB signaling, and so on pathways. Similar to lipopolysaccharide (LPS), LCWE induces the infiltration of CD11b-positive cells and inflammation in lungs. LCWE also triggers inflammatory signaling through TLR2, different from LPS through TLR4. It suggests that cytokines amplify inflammation signaling relying on NLRP3 in LCWE-induced ALI. NLRP3 deletion disrupts inflammation, IL-1β cleavage, and the infiltration of neutrophils and macrophages in the injured lung. Our study highlights an animal ALI model for Gram-positive bacterial pneumonia and that NLRP3 is a key therapeutic target to prevent inflammation and lung damage in LCWE-induced ALI.
革兰氏阳性菌肺炎是住院和死亡的重要原因。缺乏良好的实验模型和治疗靶点阻碍了急性肺损伤（ALI）的治愈。本研究利用革兰氏阳性菌干酪乳杆菌细胞壁提取物（LCWE）建立了ALI小鼠模型，并鉴定出关键调节因子NLRP3。我们发现LCWE可诱导肿瘤坏死因子（TNF）、核因子κB（NF-κB）信号等通路。与脂多糖（LPS）相似，LCWE可诱导CD11b阳性细胞浸润和肺部炎症。LCWE还通过Toll样受体2（TLR2）触发炎症信号，这与LPS通过TLR4触发炎症信号不同。这表明在LCWE诱导的ALI中，细胞因子依赖NLRP3放大炎症信号。NLRP3缺失可破坏炎症、白细胞介素-1β（IL-1β）裂解以及损伤肺组织中中性粒细胞和巨噬细胞的浸润。我们的研究突出了一种用于革兰氏阳性菌肺炎的动物ALI模型，并且NLRP3是预防LCWE诱导的ALI中炎症和肺损伤的关键治疗靶点。
