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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Nature Portfolio
2025-01-01
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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. |
format | Article |
id | doaj-art-9911419c5faa455593efbc66dbbd3122 |
institution | Kabale University |
issn | 2399-3642 |
language | English |
publishDate | 2025-01-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Communications Biology |
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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