NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus casei
Lingui Gu, Jinjin Zhu, Qingbing Nie, Binghua Xie, Shuo Xue, Ailing Zhang, Qiangwei Li, Zhengzhong Zhang, Shupeng Li, Ye Li, Qinquan Shi, Weiwei Shi, Lei Zhao, Shuzhen Liu, Xuanming Shi
Abstract
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. NLRP3 drives inflammatory signaling and cleaved IL-1β in a mouse model of acute lung injury induced by Lactobacillus casei cell wall extracts, highlighting its role as a therapeutic target in Gram-positive bacterial pneumonia.