Location: Food and Feed Safety ResearchTitle: AMPK and mTOR: Sensors and regulators of immunometabolic changes during Salmonella infection in the chicken Author
|Kogut, Michael - Mike|
|Genovese, Kenneth - Ken|
|He, Louis - Haiqi|
|Arsenault, Ryan - University Of Delaware|
Submitted to: Poultry Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2015
Publication Date: 2/26/2016
Publication URL: http://handle.nal.usda.gov/10113/62969
Citation: Kogut, M.H., Genovese, K.J., He, L.H., Arsenault, R.J. 2016. AMPK and mTOR: Sensors and regulators of immunometabolic changes during Salmonella infection in the chicken. Poultry Science. 95:345-353.
Interpretive Summary: There is a great deal of controversy concerning the use of antibiotics in animal feed. The biggest problem that critics have with this practice is the growing number of antibiotic resistant bacteria that are causing disease in humans. These bacteria appear to come from meat products. Therefore, we are interested in identifying chemicals that can protect animals from bacterial contamination without causing the bacteria to be resistant to antibiotics and other drugs that are used to treat human diseases. The purpose of these experiments was to see what kind of chemicals are produced by the immune cells when they see bacteria. We found that the immune cells produce two different chemicals that control a host response and kill the bacteria before they can hurt the chick. The results of this experiment are important to the pharmaceutical industry in the United States because we now know which chemicals are produced, or not, by the baby chick’s immune system’s cells when they see Salmonella. Thus, we can now see if there are ways for us to get the baby chick to make these chemicals which will help the chick fight Salmonella infections.
Technical Abstract: Non-typhoidal Salmonella enterica induce an early pro-inflammatory response in chickens, but the response is short-lived, asymptomatic of clinical disease, results in a persistent colonization of the gastrointestinal (GI) tract, and can transmit infections to naive hosts via fecal shedding of bacteria. The underlying mechanisms that facilitate this persistent colonization of the ceca of chickens by Salmonella are unknown. We have begun to concentrate on the convergence of metabolism and immune function as playing a major role in regulating the host responsiveness to infection. It is now recognized that the immune system monitors the metabolic state of tissues and responds by modulating metabolic function. The aim in this review is to summarize the literature that has defined a series of genotypic and phenotypic alterations in the regulatory host immune-metabolic signaling pathways in the local cecal microenvironment during the first 4 d following infection with Salmonella enterica serovar Enteritidis. Using chicken-specific kinomic immune-metabolism peptide arrays and quantitative real-time-PCR of cecal tissue during the early (4 to 48 h) and late stages (4 to 17 d) of a Salmonella infection in young broiler chickens, the local immunometabolic microenvironment has been ascertained. Distinct immune and metabolic pathways are altered between 2 to 4 d post-infection that dramatically changed the local immunometabolic environment. Thus, the tissue immunometabolic phenotype of the cecum plays a major role in the ability of the bacterium to establish a persistent cecal colonization. In general, our findings show that AMPK and mTOR are key players linking specific extracellular milieu and intracellular metabolism. Phenotypically, the early response (4 to 48 h) to Salmonella infection is pro-inflammatory, fueled by glycolysis and mTOR-mediated protein synthesis, whereas by the later phase (4 to 5 d), the local environment has undergone an immune-metabolic reprogramming to an anti-inflammatory state driven by AMPK-directed oxidative phosphorylation. Therefore, metabolism appears to provide a potential critical control point that can impact infection. Further understanding of metabolic control of immunity during infection should provide crucial information of the development of novel therapeutics based on metabolic modulators that enhance protection or inhibit infection.