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Analysis of Porcine Transcriptional Response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the Mesenteric Lymph Node
BACKGROUND: Specific knowledge of the molecular pathways controlling host-pathogen interactions can increase our understanding of immune response biology as well as provide targets for drug development and genetic improvement of disease resistance. Toward this end, we have characterized the porcine...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570369/ https://www.ncbi.nlm.nih.gov/pubmed/18811943 http://dx.doi.org/10.1186/1471-2164-9-437 |
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author | Wang, Yanfang Couture, Oliver P Qu, Long Uthe, Jolita J Bearson, Shawn MD Kuhar, Daniel Lunney, Joan K Nettleton, Dan Dekkers, Jack CM Tuggle, Christopher K |
author_facet | Wang, Yanfang Couture, Oliver P Qu, Long Uthe, Jolita J Bearson, Shawn MD Kuhar, Daniel Lunney, Joan K Nettleton, Dan Dekkers, Jack CM Tuggle, Christopher K |
author_sort | Wang, Yanfang |
collection | PubMed |
description | BACKGROUND: Specific knowledge of the molecular pathways controlling host-pathogen interactions can increase our understanding of immune response biology as well as provide targets for drug development and genetic improvement of disease resistance. Toward this end, we have characterized the porcine transcriptional response to Salmonella enterica serovar Choleraesuis (S. Choleraesuis), a Salmonella serovar that predominately colonizes swine, yet can cause serious infections in human patients. Affymetrix technology was used to screen for differentially expressed genes in pig mesenteric lymph nodes (MLN) responding to infection with S. Choleraesuis at acute (8 hours (h), 24 h and 48 h post-inoculation (pi)) and chronic stages (21 days (d) pi). RESULTS: Analysis of variance with false discovery rate control identified 1,853 genes with significant changes in expression level (p-value < 0.01, q-value < 0.26, and fold change (FC) > 2) during infection as compared to un-inoculated control pigs. Down-regulation of translation-related genes at 8 hpi and 24 hpi implied that S. Choleraesuis repressed host protein translation. Genes involved in the Th1, innate immune/inflammation response and apoptosis pathways were induced significantly. However, antigen presentation/dendritic cell (DC) function pathways were not affected significantly during infection. A strong NFκB-dependent response was observed, as 58 known NFκB target genes were induced at 8, 24 and/or 48 hpi. Quantitative-PCR analyses confirmed the microarray data for 21 of 22 genes tested. Based on expression patterns, these target genes can be classified as an "Early" group (induced at either 8 or 24 hpi) and a "Late" group (induced only at 48 hpi). Cytokine activity or chemokine activity were enriched within the Early group genes GO annotations, while the Late group was predominantly composed of signal transduction and cell metabolism annotated genes. Regulatory motif analysis of the human orthologous promoters for both Early and Late genes revealed that 241 gene promoters were predicted to contain NFκB binding sites, and that of these, 51 Early and 145 Late genes were previously not known to be NFκB targets. CONCLUSION: Our study provides novel genome-wide transcriptional profiling data on the porcine response to S. Choleraesuis and expands the understanding of NFκB signaling in response to Salmonella infection. Comparison of the magnitude and timing of porcine MLN transcriptional response to different Salmonella serovars, S. Choleraesuis and S. Typhimurium, clearly showed a larger but later transcriptional response to S. Choleraesuis. Both microarray and QPCR data provided evidence of a strong NFκB-dependent host transcriptional response during S. Choleraesuis infection. Our data indicate that a lack of strong DC-mediated antigen presentation in the MLN may cause S. Choleraesuis infected pigs to develop a systemic infection, and our analysis predicts nearly 200 novel NFκB target genes which may be applicable across mammalian species. |
format | Text |
id | pubmed-2570369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-25703692008-10-21 Analysis of Porcine Transcriptional Response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the Mesenteric Lymph Node Wang, Yanfang Couture, Oliver P Qu, Long Uthe, Jolita J Bearson, Shawn MD Kuhar, Daniel Lunney, Joan K Nettleton, Dan Dekkers, Jack CM Tuggle, Christopher K BMC Genomics Research Article BACKGROUND: Specific knowledge of the molecular pathways controlling host-pathogen interactions can increase our understanding of immune response biology as well as provide targets for drug development and genetic improvement of disease resistance. Toward this end, we have characterized the porcine transcriptional response to Salmonella enterica serovar Choleraesuis (S. Choleraesuis), a Salmonella serovar that predominately colonizes swine, yet can cause serious infections in human patients. Affymetrix technology was used to screen for differentially expressed genes in pig mesenteric lymph nodes (MLN) responding to infection with S. Choleraesuis at acute (8 hours (h), 24 h and 48 h post-inoculation (pi)) and chronic stages (21 days (d) pi). RESULTS: Analysis of variance with false discovery rate control identified 1,853 genes with significant changes in expression level (p-value < 0.01, q-value < 0.26, and fold change (FC) > 2) during infection as compared to un-inoculated control pigs. Down-regulation of translation-related genes at 8 hpi and 24 hpi implied that S. Choleraesuis repressed host protein translation. Genes involved in the Th1, innate immune/inflammation response and apoptosis pathways were induced significantly. However, antigen presentation/dendritic cell (DC) function pathways were not affected significantly during infection. A strong NFκB-dependent response was observed, as 58 known NFκB target genes were induced at 8, 24 and/or 48 hpi. Quantitative-PCR analyses confirmed the microarray data for 21 of 22 genes tested. Based on expression patterns, these target genes can be classified as an "Early" group (induced at either 8 or 24 hpi) and a "Late" group (induced only at 48 hpi). Cytokine activity or chemokine activity were enriched within the Early group genes GO annotations, while the Late group was predominantly composed of signal transduction and cell metabolism annotated genes. Regulatory motif analysis of the human orthologous promoters for both Early and Late genes revealed that 241 gene promoters were predicted to contain NFκB binding sites, and that of these, 51 Early and 145 Late genes were previously not known to be NFκB targets. CONCLUSION: Our study provides novel genome-wide transcriptional profiling data on the porcine response to S. Choleraesuis and expands the understanding of NFκB signaling in response to Salmonella infection. Comparison of the magnitude and timing of porcine MLN transcriptional response to different Salmonella serovars, S. Choleraesuis and S. Typhimurium, clearly showed a larger but later transcriptional response to S. Choleraesuis. Both microarray and QPCR data provided evidence of a strong NFκB-dependent host transcriptional response during S. Choleraesuis infection. Our data indicate that a lack of strong DC-mediated antigen presentation in the MLN may cause S. Choleraesuis infected pigs to develop a systemic infection, and our analysis predicts nearly 200 novel NFκB target genes which may be applicable across mammalian species. BioMed Central 2008-09-23 /pmc/articles/PMC2570369/ /pubmed/18811943 http://dx.doi.org/10.1186/1471-2164-9-437 Text en Copyright © 2008 Wang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Yanfang Couture, Oliver P Qu, Long Uthe, Jolita J Bearson, Shawn MD Kuhar, Daniel Lunney, Joan K Nettleton, Dan Dekkers, Jack CM Tuggle, Christopher K Analysis of Porcine Transcriptional Response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the Mesenteric Lymph Node |
title | Analysis of Porcine Transcriptional Response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the Mesenteric Lymph Node |
title_full | Analysis of Porcine Transcriptional Response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the Mesenteric Lymph Node |
title_fullStr | Analysis of Porcine Transcriptional Response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the Mesenteric Lymph Node |
title_full_unstemmed | Analysis of Porcine Transcriptional Response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the Mesenteric Lymph Node |
title_short | Analysis of Porcine Transcriptional Response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the Mesenteric Lymph Node |
title_sort | analysis of porcine transcriptional response to salmonella enterica serovar choleraesuis suggests novel targets of nfkappab are activated in the mesenteric lymph node |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570369/ https://www.ncbi.nlm.nih.gov/pubmed/18811943 http://dx.doi.org/10.1186/1471-2164-9-437 |
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