Related Experiment Video
Updated: Aug 8, 2026
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Slc6a13 Deficiency Attenuates Pasteurella multocida Infection-Induced Inflammation via Glycine-Inflammasome Signaling
Fang He1,2, Yangyang Qiu1, Xiaoyan Wu2
1College of Veterinary Medicine, Southwest University, Chongqing, China.
Abstract:
We have previously demonstrated that Slc6a13-deficient (Slc6a13-/-; KO) mice are resistant to P. multocida infection, which might be in connection with macrophage-mediated inflammation; however, the specific metabolic mechanism is still enigmatic. Here we reproduce the less sensitive to P. multocida infection in overall survival assays as well as reduced bacterial loads, tissue lesions, and inflammation of lungs in KO mice. The transcriptome sequencing analysis of wild-type (WT) and KO mice shows a large number of differentially expressed genes that are enriched in amino acid metabolism by functional analysis. Of note, glycine levels are substantially increased in the lungs of KO mice with or without P. multocida infection in comparison to the WT controls. Interestingly, exogenous glycine supplementation alleviates P. multocida infection-induced inflammation. Mechanistically, glycine reduces the production of inflammatory cytokines in macrophages by blocking the activation of inflammasome (NALP1, NLRP3, NLRC4, AIM2, and Caspase-1). Together, Slc6a13 deficiency attenuates P. multocida infection through lessening the excessive inflammatory responses of macrophages involving glycine-inflammasome signaling.
Insights
Slc6a13-deficient mice show resistance to P. multocida infection due to increased glycine levels. This amino acid dampens macrophage inflammation by inhibiting inflammasome activation, offering a potential therapeutic target.
Area of Science:
- Immunology
- Metabolic pathways
- Microbial pathogenesis
Background:
- Slc6a13-deficient (KO) mice exhibit resistance to P. multocida infection.
- The underlying metabolic mechanisms, particularly macrophage-mediated inflammation, remain unclear.
- Understanding these mechanisms is crucial for developing targeted interventions against P. multocida.
Purpose of the Study:
- To elucidate the specific metabolic mechanisms behind Slc6a13 deficiency-mediated resistance to P. multocida infection.
- To investigate the role of glycine metabolism in regulating macrophage inflammatory responses during infection.
- To explore the potential of targeting the glycine-inflammasome pathway for therapeutic benefit.
Main Methods:
- Comparative analysis of P. multocida infection susceptibility in wild-type (WT) and Slc6a13 KO mice.
- Transcriptome sequencing to identify differentially expressed genes and enriched metabolic pathways.
- Measurement of glycine levels in lung tissues and assessment of glycine supplementation effects on inflammation.
- Investigation of glycine's impact on inflammasome activation (NALP1, NLRP3, NLRC4, AIM2, Caspase-1) in macrophages.
Main Results:
- KO mice demonstrated reduced susceptibility to P. multocida, with lower bacterial loads, tissue damage, and lung inflammation.
- Transcriptomic analysis revealed significant enrichment in amino acid metabolism pathways.
- Elevated glycine levels were observed in the lungs of KO mice, irrespective of infection status.
- Exogenous glycine supplementation attenuated P. multocida-induced inflammation by inhibiting macrophage inflammasome activation.
Conclusions:
- Slc6a13 deficiency confers resistance to P. multocida infection by modulating macrophage inflammatory responses.
- Increased glycine levels in KO mice play a key role in suppressing excessive inflammation.
- The glycine-inflammasome signaling axis represents a novel therapeutic target for P. multocida infections.
More Related Videos
06:52Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
10:21Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
