1a.Objectives (from AD-416):
The current specific aims are: (1) profile the in vivo whole blood RNA and cytokine response to Salmonella Typhimurium (ST) infection in animals with high and low fecal shedding phenotypes; (2) using the same animals in Aim 1, profile the in vitro whole blood RNA and cytokine response to exposure to the general inflammatory endotoxin, lipopolysaccaride; (3) annotate response profiles for common expression patterns and functional themes and develop regulatory network information on response to inflammatory stimuli; and (4) test existing and develop improved predictive models for identifying pigs with decreased fecal shedding at multiple stages of post-infection pro and in naïve pigs.
1b.Approach (from AD-416):
Tests will be performed at BARC to quantitate RNA and protein levels for important markers of inflammatory and infectious processes critical to disease resistance. Simultaneously, the team plans to develop layers of information, based on transcriptional profiling data, on the mechanisms controlling inflammatory and infectious processes critical to disease resistance, and to integrate transcriptional and cromatin binding data available in the pig with similar data in other species to develop higher-level understanding of regulatory mechanisms.
Under this agreement samples have been collected for phenotyping pigs with superior immune responses to Salmonella infections, which would lead to decreased Salmonella shedding and pork contamination. ARS Researchers at Beltsville, MD, partnered with Iowa State University (ISU) and ARS Researchers at Ames, Iowa, to review existing data and create new data on the immediate innate response to infection with the foodborne pathogen, Salmonella typhimurium (ST). At ISU, whole blood RNA and proliferative responses of ST infected pigs with high or low fecal shedding phenotypes were compared. Response profiles have been annotated at ISU for common expression patterns, functional themes, and inflammatory regulatory networks in an effort to develop a classification tool to predict and identify pigs with a improved ST resistance, i.e., low ST fecal shedding. The classification tool should be useful for pigs post-infection but would be best if naïve pigs with low shedding of bacterial pathogens could be identified. This can be validated using experimental and field populations (samples of which are available through this project). This approach will then be tested for heritability and utility in genetic improvement to decrease Salmonella shedding and pork contamination and lead to safer pork products.