The immunometabolic responses Salmonella Enteritidis and Salmonella Heidelberg induce in chicken macrophages

Arsenault, RyanSalmonella is a burden to the agriculture and health sectors as a result of the high number of illnesses, food contamination, and recalls. Salmonella Enteritidis (S. Enteritidis) is one of the most prevalent serotypes isolated from poultry. Salmonella Heidelberg (S. Heidelberg), which is becoming more prevalent than S. Enteritidis, is one of the five most isolated serotypes. Many animals including poultry are carriers of Salmonella but do not show any symptoms. Thus, it is more difficult for producers to avoid the processing and the distribution of contaminated products especially due to the restriction of antibiotic use in food animals. Salmonella invades host cells and exploits host mechanisms for its own benefits. For example, Salmonellae are capable of surviving in macrophages whose role is to kill pathogenic bacteria. Understanding the mechanism by which Salmonella infects and creates a suitable niche in hosts will reveal a potential target for the treatment and prevention of Salmonella contamination without the use of antibiotics. Although S. Enteritidis and S. Heidelberg are almost genetically identical, they both are capable of inducing different immune and metabolic responses in host cells to successfully establish an infection. Kinome peptide array data and available literature showed significant changes in the phosphorylation states of mTOR and AMPK peptides in chickens during Salmonella infections. Therefore, focusing on the AMPK-mTOR signaling cascade, we demonstrated that S. Enteritidis and S. Heidelberg infections induced differential kinase activities in metabolic and immune related peptides of HD11 chicken macrophages. Metabolic flux assays measuring extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) demonstrated that, i) S. Enteritidis at 30 minutes post infection increased glucose metabolism ii) S. Heidelberg at 30 minutes post infection decreased glucose metabolism iii) Both Salmonella infections induce increased oxygen metabolism. Gentamicin protection assays performed at 30 minutes and 2 hours post infection revealed that S. Enteritidis bacteria are more invasive than S. Heidelberg. Furthermore, flow cytometry results showed increased apoptotic/dead cell population in S. Enteritidis infections compared to S. Heidelberg. These results show different immunometabolic responses of HD11 macrophages to S. Enteritidis and S. Heidelberg infections.University of Delaware, Department of Biological SciencesM.S