Location: Food and Feed Safety Research
Project Number: 3091-32000-034-00-D
Project Type: In-House Appropriated
Start Date: Jan 3, 2016
End Date: Aug 8, 2017
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.
Poultry meat products are a major source of human foodborne illness caused by Salmonella and Campylobacter. With poultry producers under increasing pressure to reduce their use of antibiotics to control disease and enhance production, the development of cost-effective, pre-harvest immunological interventions to reduce these microbial pathogens in poultry products would be of great value to the food industry and to the consumer. Immune modulation is one approach for new anti-infective therapies, whereby natural mechanisms in the host can be exploited to strengthen therapeutic benefit. The stimulation of innate immunity has considerable potential to induce a profound and rapid cross-protection against multiple serovars of bacteria. Using "omic" techniques, including functional genomics, epigenetics, proteomics, and metabolomics, we will identify effective modulators of innate immunity to control infections, especially in situations where vaccination is not appropriate. Further, metabolism and host immunity are essential requirements for survival. Mounting an immune response requires major changes to metabolic processes. Thus, the integration of central metabolic pathways and nutrient sensing with antibacterial immunity alters cellular energy homeostasis and contributes to the prevention or resolution of infectious diseases. Hence, immune and metabolic response processes govern infectious diseases. A greater understanding of the critical nodes of immunometabolism during Salmonella and Campylobacter infections will provide opportunities to break the tight connection of defects in metabolism and immunity that propagate persistent infections resulting in improved safety of food products without the use of antibiotics.