Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 7/5/2007
Publication Date: 8/10/2007
Citation: Lunney, J.K., Bearson, S.M., Wang, Y.F., Uthe, J.J., Qu, K., Couture, O.P., Zhao, S.H., Kuhar, D.J., Nettleton, D., Dekkers, J.C., Tuggle, C.K. 2007. Comparative immune responses of pigs to infection with Salmonella enterica serovars of food safety (Typhimurium) and animal health (Choleraesuis)importance. Proceedings 8th Intl Veterinary Immunology Symposium, Ouro Preto, Brazil. p. 49-50.
Technical Abstract: Salmonella infections cause food safety concerns for humans as well as production problems for swine. Our team has used suppression hybridization (SSH), long oligonucleotide Qiagen and Affymetrix porcine GeneChip® arrays, and real time gene expression (Q-PCR) to understand the host response to, and control of, S. enterica serotype Typhimurium (ST) as compared to S. enterica serotype Choleraesuis (SC). We identified differentially expressed (DE) genes in mesenteric lymph nodes (MLN) and lungs of pigs with acute [8, 24, 48 hours post-inoculation (hpi)], and chronic stages [7, 21 days (dpi)] of infection. The SSH analyses identified several genes involved in heat shock response and cytoskeletal rearrangements. Hierarchical gene cluster and pathway analyses of the microarray data revealed that host protein translation was repressed by both pathogens, with an especially strong transcriptional response at 48 hpi with SC. A high proportion of significantly up-regulated DE genes in both infections are involved in pathways for immune T helper 1 (Th1) differentiation, innate immune/inflammatory responses and antigen processing. Gene expression induction was weaker and occurred earlier in ST (24 hpi) as compared to SC. In SC the response was maximal at 48 hpi but continued to be elevated at 7 dpi. This differential transcriptional response was mirrored by interferon gamma and tumor necrosis factor serum protein levels as well as bacterial load in the lymph nodes. Apoptosis and antigen presentation/dendritic cell function pathways were down-regulated at 8 hpi for ST. Cluster analyses, confirmed by Q-PCR analyses, revealed that many DE genes grouped into a specific induced sub-cluster are known NFkB targets. Suppression of NFkB signaling from 24 to 48 hpi may allow ST to elude an anti-bacterial inflammatory reaction. Studies are underway to study Salmonella-cell culture invasion further using IPEC J2 epithelial cells derived from porcine small intestine. We propose that NFkB suppression in antigen presenting cells may be a mechanism by which ST eludes a strong inflammatory response, thus setting the stage for establishing a carrier status in pigs. For SC infections, there was a strong NFkB-dependent transcriptional response and a more intense and extended up-regulation of porcine immune gene expression, potentially resulting in clearance of the SC infection.