REV-ERBα negatively regulates NLRP6 transcription and reduces the severity of Salmonella infection in mice
Non-typhoidal Salmonella infection is among the most frequent foodborne diseases threatening human health worldwide. The host circadian clock orchestrates daily rhythms to adapt to environmental changes, including coordinating immune function in response to potential infections. However, the molecul...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024044633 |
| _version_ | 1797213405343383552 |
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| author | Lanqing Sun Kai Huang Qifeng Deng Yuan Zhu Yu Cao Kedi Dong Sidi Yang Yuanyuan Li Shuyan Wu Rui Huang |
| author_facet | Lanqing Sun Kai Huang Qifeng Deng Yuan Zhu Yu Cao Kedi Dong Sidi Yang Yuanyuan Li Shuyan Wu Rui Huang |
| author_sort | Lanqing Sun |
| collection | DOAJ |
| description | Non-typhoidal Salmonella infection is among the most frequent foodborne diseases threatening human health worldwide. The host circadian clock orchestrates daily rhythms to adapt to environmental changes, including coordinating immune function in response to potential infections. However, the molecular mechanisms underlying the interplay between the circadian clock and the immune system in modulating infection processes are incompletely understood. Here, we demonstrate that NLRP6, a novel nucleotide-oligomerization domain (NOD)-like receptor (NLR) family member highly expressed in the intestine, is closely associated with the differential day–night response to Salmonella infection. The core clock component REV-ERBα negatively regulates NLRP6 transcription, leading to the rhythmic expression of NLRP6 and the secretion of IL-18 in intestinal epithelial cells, playing a crucial role in mediating the differential day–night response to Salmonella infection. Activating REV-ERBα with agonist SR9009 in wild-type mice attenuated the severity of infection by decreasing the NLRP6 level in intestinal epithelial cells. Our findings provide new insights into the association between the host circadian clock and the immune response to enteric infections by revealing the regulation of Salmonella infection via the inhibitory effect of REV-ERBα on NLRP6 transcription. Targeting REV-ERBα to modulate NLRP6 activation may be a potential therapeutic strategy for bacterial infections. |
| first_indexed | 2024-04-24T10:57:45Z |
| format | Article |
| id | doaj.art-ba567c04c51f4ae0a42ba2231f4a07dc |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T10:57:45Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-ba567c04c51f4ae0a42ba2231f4a07dc2024-04-12T04:45:29ZengElsevierHeliyon2405-84402024-04-01108e28432REV-ERBα negatively regulates NLRP6 transcription and reduces the severity of Salmonella infection in miceLanqing Sun0Kai Huang1Qifeng Deng2Yuan Zhu3Yu Cao4Kedi Dong5Sidi Yang6Yuanyuan Li7Shuyan Wu8Rui Huang9Department of Medical Microbiology, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123 Jiangsu, PR China; Department of Laboratory Medicine, Affiliated Hospital of Jiangnan University, Wuxi, 214000 Jiangsu, PR ChinaOrthopaedic Institute, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi, 214062 Jiangsu, PR China; Cambridge–Suda Genomic Resource Center, Jiangsu Key Laboratory of Neuropsychiatric Diseases, Suzhou Medical College of Soochow University, Suzhou, 215123 Jiangsu, PR ChinaMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 Guangdong, PR ChinaDepartment of Medical Microbiology, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123 Jiangsu, PR China; Department of Laboratory Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, 315010 Zhejiang, PR ChinaDepartment of Medical Microbiology, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123 Jiangsu, PR China; Laboratory Department, Children's Hospital of Soochow University, Suzhou, 215025 Jiangsu, PR ChinaDepartment of Medical Microbiology, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123 Jiangsu, PR China; Department of Blood Transfusion, The First Affiliated Hospital of Ningbo University, Ningbo, 315010 Zhejiang, PR ChinaGuangzhou National Laboratory, Guangzhou International BioIsland, Guangzhou, 510005 Guangdong, PR ChinaDepartment of Medical Microbiology, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123 Jiangsu, PR ChinaDepartment of Medical Microbiology, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123 Jiangsu, PR China; Corresponding author.Department of Medical Microbiology, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123 Jiangsu, PR China; Corresponding author.Non-typhoidal Salmonella infection is among the most frequent foodborne diseases threatening human health worldwide. The host circadian clock orchestrates daily rhythms to adapt to environmental changes, including coordinating immune function in response to potential infections. However, the molecular mechanisms underlying the interplay between the circadian clock and the immune system in modulating infection processes are incompletely understood. Here, we demonstrate that NLRP6, a novel nucleotide-oligomerization domain (NOD)-like receptor (NLR) family member highly expressed in the intestine, is closely associated with the differential day–night response to Salmonella infection. The core clock component REV-ERBα negatively regulates NLRP6 transcription, leading to the rhythmic expression of NLRP6 and the secretion of IL-18 in intestinal epithelial cells, playing a crucial role in mediating the differential day–night response to Salmonella infection. Activating REV-ERBα with agonist SR9009 in wild-type mice attenuated the severity of infection by decreasing the NLRP6 level in intestinal epithelial cells. Our findings provide new insights into the association between the host circadian clock and the immune response to enteric infections by revealing the regulation of Salmonella infection via the inhibitory effect of REV-ERBα on NLRP6 transcription. Targeting REV-ERBα to modulate NLRP6 activation may be a potential therapeutic strategy for bacterial infections.http://www.sciencedirect.com/science/article/pii/S2405844024044633Salmonella TyphimuriumCircadian clockNLRP6REV-ERBαIntestinal epithelial cell |
| spellingShingle | Lanqing Sun Kai Huang Qifeng Deng Yuan Zhu Yu Cao Kedi Dong Sidi Yang Yuanyuan Li Shuyan Wu Rui Huang REV-ERBα negatively regulates NLRP6 transcription and reduces the severity of Salmonella infection in mice Heliyon Salmonella Typhimurium Circadian clock NLRP6 REV-ERBα Intestinal epithelial cell |
| title | REV-ERBα negatively regulates NLRP6 transcription and reduces the severity of Salmonella infection in mice |
| title_full | REV-ERBα negatively regulates NLRP6 transcription and reduces the severity of Salmonella infection in mice |
| title_fullStr | REV-ERBα negatively regulates NLRP6 transcription and reduces the severity of Salmonella infection in mice |
| title_full_unstemmed | REV-ERBα negatively regulates NLRP6 transcription and reduces the severity of Salmonella infection in mice |
| title_short | REV-ERBα negatively regulates NLRP6 transcription and reduces the severity of Salmonella infection in mice |
| title_sort | rev erbα negatively regulates nlrp6 transcription and reduces the severity of salmonella infection in mice |
| topic | Salmonella Typhimurium Circadian clock NLRP6 REV-ERBα Intestinal epithelial cell |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024044633 |
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