Associations of the porcine immune response and genetic polymorphisms with the shedding of Salmonella enterica serovar Typhimurium Searson, s: 111 , Uthe, J. 1121 , Wang, Y.(2), Qu, L.(2), De kkers, J. 12 · 31 , Nettleton, 0 . 13 • 4 >, Searson, S. 151 , Tuggle, c.< 2 • 3 > 111 USOA, ARS, Nallonal An1mal D1sease Center, Ames, lA, 50010, USA 1 21 Department of Animal Science, Iowa State University, Ames, lA, 50011, USA 131 Center for Integrated An1mal Genom1cs , Iowa State Un1vers1ty, Ames, lA, 50011 , USA 141 Department of Statistics, Iowa State Un1versity, Ames. lA, 50011, USA 151 USOA, ARS, National So1l Tilth Lab, Ames, lA 50011 USA Shawn MD Bearson sbearson@nadc.ars.usda.gov Abstract A major focus of our collaborattve research 1s to 1nvest1gate the porctne response to Infection w1th Salmonella to 1) identify porctne genes differentially regulated during Infection and 2) Identify and associate genetic polymorphisms within these genes with infect1on status across swine populat1ons In the current study, 40 crossbred p1gs were intranasally Inoculated with Salmonella enterica serovar Typh1murium and mon1tored for Salmonella fecal shedding and blood 1mmune parameters at 2, 7, 14 and 20 days post-inoculation (dpi). Using a multivariate permutation test, a posit1ve correlation was observed between Salmonella shedding and Interferon-gamma (IFNG) levels at 2 and 7 dpi (p<0.05), w1th a greater number of Salmonella shedding 1n the an1mals w1th higher IFNG levels In addit1on, a positive correlation was observed between IFNG levels and the number of c1rculat1ng neutroph1ls at 7 and 14 dpi, mature banded neutroph1ls at 2 dp1, monocytes at 7 dp1 and wh1te blood cells (WBCs) at 7, 14 and 20 dp1. We have further performed assoc1atton studies of immune response parameters or shedding status of the Salmonella-Infected p1gs with single nucleotide polymorphisms (SNPs) in 9 genes· VCP, CCT7, LCP1, C047, SCARB2, CD163, CCR1 , TLR4 and TYROBP Express1on of these genes was 1dent1fied by our group as differentially-regulated during Salmonella infection, and assays for these SNPs have been developed 1n our laboratones. Specifically, preliminary analysis suggests a posttive assoc1at1on (p<O 05) of SNP genotype AJG at nucleotide 1026 (relative to start codon) of the CCT7 gene wtth circulating neutroph1ls and WBCs and with Salmonella shedd1ng at 7 dp1 compared to the G/G heterozygote genotype CCT7 encodes a molecular chaperone involved in tubulin folding and protection Thus, our analyses are ltnk1ng the porctne 1mmune response to Salmonella 1nfect1on with specific genes and genet1c polymorphisms, thereby providing potential markers for carrier pigs as well as targets for disease d1agnos1s , tntervent1on and prevention Introduct i on Currently the most frequently applied methods for d1sease control in livestock involve the use of antibiotic drugs and/or vaccines However these approaches are not always effecllve (1 ). furthermore. antibiotic use is being regulated more stnctly and may be banned from food products tn the future Th1s creates a real need for altemat1ve approaches to disease control to protect the food supply One such approach 1s the identification and use of an1mals w1th enhanced d1sease resistance If genes can be identified from antmals which are naturally more res1stant to microorgantsms (such as Salmonella) direct Improvement in food safety as well as antmal disease can be ach1eved by selecting favorable animals to breed disease-resistant offspring A major problem in pre-harvest food safety is contamination on the farm or slaughter plant enwonment by an1mals sheddtng pathogenic bacteria such as Salmonella entenca (2 3) An additional challenge is the difficulty in 1dent1fying wh1ch animals are carriers and therefore will 1n tum be shedders Stnce the current technology IS not ent1rely effic1ent in detecttng Salmonella- tnfected p1gs the goal of th is study was to investigate specific molecular parameters for their 413