Investigation of Immunoregulation in Reducing Foodborne Pathogen Colonization in Poultry

Objective 1: Define the differential host-pathogen interactions between Salmonella and chicken and poultry mucosal immune systems using genomic technologies. Sub-objective 1.A. Screen two lines of chickens and turkeys to identify individual sires and dams that have inherently higher and lower levels of key pro-inflammatory cytokines/chemokines (IL-6, CXCLi2, and CCLi1) and perform specific matings to produce a high and low line of chickens/turkeys and evaluate this novel selection method for increased resistance against Salmonella enterica serovar Enteritidis. Sub-objective 1.B. Evaluate the mucosal immune response and gut microbiome in differentially selected immune lines of chickens and turkeys. Objective 2: Determine the relationship between foodborne pathogens and the mucosal innate immune response focusing on epigenetic reprogramming of host immune genes in persistent infections. Objective 3: Develop new vaccination strategies based on innate immunity to reduce Salmonella
contamination in broiler chickens and turkeys. Objective 4: Develop strategies to reduce foodborne pathogens by targeting host immune-metabolic signaling pathways affected by Salmonella and Campylobacter virulence factors. Sub-objective 4.A. Characterize the immune-metabolic pathways through which Salmonella and Campylobacter infection induce a local "tolerogenic" environment in the intestine that controls T regulatory cell development and mediates long-term persistent infection. Sub-objective 4.B. Characterize the immune-metabolic signaling pathways in the ceca of chickens and turkeys treated with various immune modulators that protect birds against Salmonella and Campylobacter infections. Objective 5: Analyze and characterize both host and Salmonella proteins that are modulated in expression during infection using quantitative proteomics. Sub-objective 5.A. Construct a Salmonella proteomic array to identify common Salmonella-specific antigen targets using immune sera from chickens
and turkeys infected with different serovars of Salmonella. Sub-objective 5.B. Develop a high-throughput assay to screen small molecules for their ability to inhibit virulence factors produced by various serovars of Salmonella enterica.