Location: Food and Feed Safety ResearchTitle: M2 polarization and inhibition of host cell glycolysis contributes intracellular survival of Salmonella strains in chicken macrophage HD-11 cells
|He, Louis - Haiqi|
|Genovese, Kenneth - Ken|
|ARSENAULT, RYAN - University Of Delaware|
|Swaggerty, Christina - Christi|
|Byrd Ii, James - Allen|
|Kogut, Michael - Mike|
Submitted to: Microorganisms
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/18/2023
Publication Date: 7/19/2023
Citation: He, L.H., Genovese, K.J., Arsenault, R.J., Johnson, C.N., Swaggerty, C.L., Byrd II, J.A., Kogut, M.H. 2023. M2 polarization and inhibition of host cell glycolysis contributes intracellular survival of Salmonella strains in chicken macrophage HD-11 cells. Microorganisms. 11(7). Article 1838. https://doi.org/10.3390/microorganisms11071838.
Interpretive Summary: Salmonella are the most common foodborne pathogens from poultry and are often associated with human salmonellosis. Macrophage cells are one of the white blood cells that can produce chemicals to kill bacteria. In this study, we used tools of kinomic array and cell metabolic analyzsis to study the change of glucose metabolism in chicken macrophage cells when infected by Salmonella. Our results show that Salmonella infection causes significant change in macrophage cell glucose metabolism. This change plays an important role in the immune function of chicken macrophage cells and strongly affects bacterial survival inside the cells. Our findings are important to the poultry industries in the United States and will offer new knowledge in controlling Salmonella in poultry.
Technical Abstract: Salmonella enterica is a group of facultative, gram-negative bacteria. Recently, new evidence indicated that Salmonella could reprogram the host metabolism to increase energy or metabolites available for intracellular replication. In this study, using a chicken-specific kinomic immunometabolism peptide array analysis, we found that infection by S. Enteritidis induced significant phosphorylation changes in many key proteins of the glycolytic pathway in chicken macrophage HD-11 cells, indicating a shift in glycolysis caused by Salmonella infection. Nitric oxide (NO) production and changes of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) represented by extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), respectively, were measured in chicken macrophages infected with three Salmonella strains (S. Enteritidis, S. Heidelberg, and S. Senftenberg). The infection reduced glycolysis and enhanced OXPHOS in chicken macrophages as indicated by changes of ECAR and OCR. Salmonella strains differentially affected macrophage polarization and glycolysis. Among three strains tested, S. Enteritidis was most effective in downregulating glycolysis and promoting M2 polarization as measured by ECAR, ORC, and NO production; while S. Senftenberg did not alter glycolysis and may promote M1 polarization. Our results suggested that downregulation of host cell glycolysis and increase of M2 polarization of macrophages may contribute to increased intracellular survival of Salmonella.