NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus casei

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...

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Main Authors: Lingui Gu, Jinjin Zhu, Qingbing Nie, Binghua Xie, Shuo Xue, Ailing Zhang, Qiangwei Li, Zhengzhong Zhang, Shupeng Li, Yusen Li, Qinquan Shi, Weiwei Shi, Lei Zhao, Shuzhen Liu, Xuanming Shi
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07462-9
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author Lingui Gu
Jinjin Zhu
Qingbing Nie
Binghua Xie
Shuo Xue
Ailing Zhang
Qiangwei Li
Zhengzhong Zhang
Shupeng Li
Yusen Li
Qinquan Shi
Weiwei Shi
Lei Zhao
Shuzhen Liu
Xuanming Shi
author_facet Lingui Gu
Jinjin Zhu
Qingbing Nie
Binghua Xie
Shuo Xue
Ailing Zhang
Qiangwei Li
Zhengzhong Zhang
Shupeng Li
Yusen Li
Qinquan Shi
Weiwei Shi
Lei Zhao
Shuzhen Liu
Xuanming Shi
author_sort Lingui Gu
collection DOAJ
description 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.
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institution Kabale University
issn 2399-3642
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publishDate 2025-01-01
publisher Nature Portfolio
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spelling doaj-art-9911419c5faa455593efbc66dbbd31222025-01-12T12:35:42ZengNature PortfolioCommunications Biology2399-36422025-01-018111310.1038/s42003-025-07462-9NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus caseiLingui Gu0Jinjin Zhu1Qingbing Nie2Binghua Xie3Shuo Xue4Ailing Zhang5Qiangwei Li6Zhengzhong Zhang7Shupeng Li8Yusen Li9Qinquan Shi10Weiwei Shi11Lei Zhao12Shuzhen Liu13Xuanming Shi14The School of Basic Medical Sciences, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe Fuyang Hospital, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe First Affiliated Hospital, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe Fuyang Hospital, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityThe School of Basic Medical Sciences, Anhui Medical UniversityAbstract 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.https://doi.org/10.1038/s42003-025-07462-9
spellingShingle Lingui Gu
Jinjin Zhu
Qingbing Nie
Binghua Xie
Shuo Xue
Ailing Zhang
Qiangwei Li
Zhengzhong Zhang
Shupeng Li
Yusen Li
Qinquan Shi
Weiwei Shi
Lei Zhao
Shuzhen Liu
Xuanming Shi
NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus casei
Communications Biology
title NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus casei
title_full NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus casei
title_fullStr NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus casei
title_full_unstemmed NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus casei
title_short NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus casei
title_sort nlrp3 promotes inflammatory signaling and il 1β cleavage in acute lung injury caused by cell wall extract of lactobacillus casei
url https://doi.org/10.1038/s42003-025-07462-9
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