Affiliation:
1. Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China
2. Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Jinan 250100, China
3. School of Life Sciences, Shandong Normal University, Jinan 250014, China
4. Shandong Center for Quality Control of Feed and Veterinary Drug, Jinan 250100, China
Abstract
Glaesserella parasuis (G. parasuis), an important pathogenic bacterium, cause Glässer’s disease, and has resulted in tremendous economic losses to the global swine industry. G. parasuis infection causes typical acute systemic inflammation. However, the molecular details of how the host modulates the acute inflammatory response induced by G. parasuis are largely unknown. In this study, we found that G. parasuis LZ and LPS both enhanced the mortality of PAM cells, and at the same time, the level of ATP was enhanced. LPS treatment significantly increased the expressions of IL-1β, P2X7R, NLRP3, NF-κB, p-NF-κB, and GSDMD, leading to pyroptosis. Furthermore, these proteins’ expression was enhanced following extracellular ATP further stimulation. When reduced the production of P2X7R, NF-κB-NLRP3-GSDMS inflammasome signaling pathway was inhibited, and the mortality of cells was reduced. MCC950 treatment repressed the formation of inflammasome and reduced mortality. Further exploration found that the knockdown of TLR4 significantly reduced ATP content and cell mortality, and inhibited the expression of p-NF-κB and NLRP3. These findings suggested upregulation of TLR4-dependent ATP production is critical for G. parasuis LPS-mediated inflammation, provided new insights into the molecular pathways underlying the inflammatory response induced by G. parasuis, and offered a fresh perspective on therapeutic strategies.
Funder
National Key Research and Development Program of China
National Natural Science Funds
Project of Natural Science Foundation of Shandong Province
Key R&D Program of Shandong Province, China
Shandong Provincial Modern Agricultural Industry and Technology System
Agricultural Science and Technology Innovation Project of Shandong Academy of Agricultural Sciences