Author
WANG, YAN - ISU | |
QU, LONG - ISU | |
UTHE, JOLITA - ISU | |
Bearson, Shawn | |
Kuhar, Daniel | |
Lunney, Joan | |
COUTURE, OLIVER - ISU | |
NETTLETON, DAN - ISU | |
DEKKERS, JACK - ISU | |
TUGGLE, CHRISTOPHER - ISU |
Submitted to: Genomics
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 5/17/2007 Publication Date: 5/17/2007 Citation: Wang, Y.F., Qu, L., Uthe, J.J., Bearson, S.M., Kuhar, D.J., Lunney, J.K., Couture, O.P., Nettleton, D., Dekkers, J.C., Tuggle, C.K. 2007. Global transcriptional response of porcine mesenteric lymph nodes to Salmonella enterica serovar Typhimurium. Genomics. 90(1):72-84. Interpretive Summary: Infection with Salmonella enterica causes inflammation of the stomach and intestines in both humans and pigs. Pigs infected with Salmonella can develop a subclinical infection (carrier state), whereby the pigs shed Salmonella in their feces but do not show signs of disease. Therefore, Salmonella-shedding pigs are a food safety concern and animal health issue. This study examined the response of the gastrointestinal lymph nodes of pigs during infection with Salmonella enterica serovar Typhimurium. The results indicated that a key immune response system (NF'B) was suppressed during infection. Suppression of the NF'B system may provide a strategy for Salmonella enterica serovar Typhimurium to evade a strong immune response by the pig. This immune evasion could contribute to the ability of serovar Typhimurium to establish a subclinical (carrier) infection in the pig. This information will be helpful in developing or improving Salmonella infection control strategies that boost the immune response of the pig, such as vaccination, immunomodulation or selective pig breeding for resistance to Salmonella. Technical Abstract: Salmonellosis is prevalent worldwide and is both a food safety and animal production problem. To understand the host transcriptional response to Salmonella enterica serovar Typhimurium, the Affymetrix GeneChip® porcine genome array was used to identify differentially expressed (DE) genes in mesenteric lymph nodes (MLN) responding to infection at 8 hours post-inoculation (hpi), 24hpi, 48hpi, and 21 days post-inoculation (dpi). The expression of 16,229 transcripts was detected during infection, and 848 of these genes were differentially expressed (p<0.01, fold change >2, q<0.24). Compared to the overall transcriptome, a considerable proportion of the DE genes were assigned GO terms involving immune response, inflammatory response and defense response. No significant changes in gene expression were observed for several cell-type markers, indicating cell migration probably does not explain the expression differences. Pathway analyses showed that T helper 1 (Th1), innate/inflammatory and antigen processing pathways were induced at 24 and/or 48 hpi, while apoptosis and antigen presentation/dendritic cell function pathways were down-regulated at 8 hpi during infection. DE gene cluster analyses identified 10 sub-clusters. Most cytokine, chemokine, IFNG-induced and NF'B target genes were grouped into specific induced sub-clusters, and some translation related genes were found in a repressed sub-cluster. Q-PCR analysis confirmed Affymetrix results that revealed a transcriptional induction of NF'B target genes at 24 hpi and suppression of the NF'B pathway from 24 to 48 hpi. We propose that such NF'B suppression in antigen presenting cells might be the mechanism by which S. Typhimurium eludes a strong inflammatory response to establish a carrier status in swine. |