Exogenous L-Serine Alleviates <i>Pasteurella multocida</i>-Induced Inflammation by Reprogramming the Transcription and Metabolism of Macrophages
<i>P. multocida</i> is notorious for inducing excessive inflammation with high lethality in multiple animals, such as cattle, pigs, and chickens. Our previous study revealed that L-serine was decreased in the lungs of mice infected with <i>P. multocida</i> capsular type A str...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Veterinary Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2306-7381/12/3/254 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850277467752759296 |
|---|---|
| author | Fang He Zhengchun Lang Yanlan Huang Yangyang Qiu Pan Xiong Nengzhang Li Guangfu Zhao Yuanyi Peng |
| author_facet | Fang He Zhengchun Lang Yanlan Huang Yangyang Qiu Pan Xiong Nengzhang Li Guangfu Zhao Yuanyi Peng |
| author_sort | Fang He |
| collection | DOAJ |
| description | <i>P. multocida</i> is notorious for inducing excessive inflammation with high lethality in multiple animals, such as cattle, pigs, and chickens. Our previous study revealed that L-serine was decreased in the lungs of mice infected with <i>P. multocida</i> capsular type A strain CQ2 (PmCQ2), and 2 mg/kg of L-serine could alleviate PmCQ2-induced lung inflammation in vivo, which may largely depend on macrophages. However, the underlying intrinsic alterations remain unknown. Here, we demonstrated that 10 mM of L-serine significantly inhibited the release of inflammatory cytokines (e.g., IL-1β and TNF-α) by blocking inflammasome activation (including NALP1, NLRP3, NLRC4, AIM2, and Caspase-1) in PmCQ2-infected macrophages. Furthermore, the results of RNA-seq and metabonomics revealed that exogenous L-serine supplementation substantially reprogrammed macrophage transcription and metabolism. Mechanically, L-serine reduced inflammatory responses via the inhibition of glycolysis in macrophages based on a seahorse assay. Together, these findings characterize the intrinsic molecular alterations in activated macrophages and provide new targets for modulating <i>P. multocida</i> infection-induced macrophage inflammation. |
| format | Article |
| id | doaj-art-deec2f5553d44ec2b45384452d040757 |
| institution | OA Journals |
| issn | 2306-7381 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Veterinary Sciences |
| spelling | doaj-art-deec2f5553d44ec2b45384452d0407572025-08-20T01:49:53ZengMDPI AGVeterinary Sciences2306-73812025-03-0112325410.3390/vetsci12030254Exogenous L-Serine Alleviates <i>Pasteurella multocida</i>-Induced Inflammation by Reprogramming the Transcription and Metabolism of MacrophagesFang He0Zhengchun Lang1Yanlan Huang2Yangyang Qiu3Pan Xiong4Nengzhang Li5Guangfu Zhao6Yuanyi Peng7College of Veterinary Medicine, Southwest University, Chongqing 400715, ChinaCollege of Veterinary Medicine, Southwest University, Chongqing 400715, ChinaCollege of Veterinary Medicine, Southwest University, Chongqing 400715, ChinaCollege of Veterinary Medicine, Southwest University, Chongqing 400715, ChinaCollege of Veterinary Medicine, Southwest University, Chongqing 400715, ChinaCollege of Veterinary Medicine, Southwest University, Chongqing 400715, ChinaCollege of Veterinary Medicine, Southwest University, Chongqing 400715, ChinaCollege of Veterinary Medicine, Southwest University, Chongqing 400715, China<i>P. multocida</i> is notorious for inducing excessive inflammation with high lethality in multiple animals, such as cattle, pigs, and chickens. Our previous study revealed that L-serine was decreased in the lungs of mice infected with <i>P. multocida</i> capsular type A strain CQ2 (PmCQ2), and 2 mg/kg of L-serine could alleviate PmCQ2-induced lung inflammation in vivo, which may largely depend on macrophages. However, the underlying intrinsic alterations remain unknown. Here, we demonstrated that 10 mM of L-serine significantly inhibited the release of inflammatory cytokines (e.g., IL-1β and TNF-α) by blocking inflammasome activation (including NALP1, NLRP3, NLRC4, AIM2, and Caspase-1) in PmCQ2-infected macrophages. Furthermore, the results of RNA-seq and metabonomics revealed that exogenous L-serine supplementation substantially reprogrammed macrophage transcription and metabolism. Mechanically, L-serine reduced inflammatory responses via the inhibition of glycolysis in macrophages based on a seahorse assay. Together, these findings characterize the intrinsic molecular alterations in activated macrophages and provide new targets for modulating <i>P. multocida</i> infection-induced macrophage inflammation.https://www.mdpi.com/2306-7381/12/3/254L-serine<i>Pasteurella multocida</i>macrophageinflammasomemetabolic reprogramming |
| spellingShingle | Fang He Zhengchun Lang Yanlan Huang Yangyang Qiu Pan Xiong Nengzhang Li Guangfu Zhao Yuanyi Peng Exogenous L-Serine Alleviates <i>Pasteurella multocida</i>-Induced Inflammation by Reprogramming the Transcription and Metabolism of Macrophages Veterinary Sciences L-serine <i>Pasteurella multocida</i> macrophage inflammasome metabolic reprogramming |
| title | Exogenous L-Serine Alleviates <i>Pasteurella multocida</i>-Induced Inflammation by Reprogramming the Transcription and Metabolism of Macrophages |
| title_full | Exogenous L-Serine Alleviates <i>Pasteurella multocida</i>-Induced Inflammation by Reprogramming the Transcription and Metabolism of Macrophages |
| title_fullStr | Exogenous L-Serine Alleviates <i>Pasteurella multocida</i>-Induced Inflammation by Reprogramming the Transcription and Metabolism of Macrophages |
| title_full_unstemmed | Exogenous L-Serine Alleviates <i>Pasteurella multocida</i>-Induced Inflammation by Reprogramming the Transcription and Metabolism of Macrophages |
| title_short | Exogenous L-Serine Alleviates <i>Pasteurella multocida</i>-Induced Inflammation by Reprogramming the Transcription and Metabolism of Macrophages |
| title_sort | exogenous l serine alleviates i pasteurella multocida i induced inflammation by reprogramming the transcription and metabolism of macrophages |
| topic | L-serine <i>Pasteurella multocida</i> macrophage inflammasome metabolic reprogramming |
| url | https://www.mdpi.com/2306-7381/12/3/254 |
| work_keys_str_mv | AT fanghe exogenouslserinealleviatesipasteurellamultocidaiinducedinflammationbyreprogrammingthetranscriptionandmetabolismofmacrophages AT zhengchunlang exogenouslserinealleviatesipasteurellamultocidaiinducedinflammationbyreprogrammingthetranscriptionandmetabolismofmacrophages AT yanlanhuang exogenouslserinealleviatesipasteurellamultocidaiinducedinflammationbyreprogrammingthetranscriptionandmetabolismofmacrophages AT yangyangqiu exogenouslserinealleviatesipasteurellamultocidaiinducedinflammationbyreprogrammingthetranscriptionandmetabolismofmacrophages AT panxiong exogenouslserinealleviatesipasteurellamultocidaiinducedinflammationbyreprogrammingthetranscriptionandmetabolismofmacrophages AT nengzhangli exogenouslserinealleviatesipasteurellamultocidaiinducedinflammationbyreprogrammingthetranscriptionandmetabolismofmacrophages AT guangfuzhao exogenouslserinealleviatesipasteurellamultocidaiinducedinflammationbyreprogrammingthetranscriptionandmetabolismofmacrophages AT yuanyipeng exogenouslserinealleviatesipasteurellamultocidaiinducedinflammationbyreprogrammingthetranscriptionandmetabolismofmacrophages |