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Peripheral blood transcriptome is an important intermediate data source for investigating the mechanism of Salmonella invasion, proliferation, and transmission. We challenged 4-week old piglets with Salmonella enterica serovar Typhimurium LT2 and investigated the peripheral blood gene expression profile before treatment (d0) and at 2 and 7 days post-inoculation (dpi) using deep sequencing. Regulator pathways were first predicted in silico and validated by wet-lab experiments. In total, 1255, 765, and 853 genes were differentially expressed between 2 dpi/d0, 7 dpi/d0, and 7 dpi/2 dpi, respectively. Additionally, 1333 genes showed a time effect during the investigated Salmonella infection period. Clustering analysis showed that the differentially expressed genes fell into six distinct expression clusters. Pathway annotation of these gene clusters showed that the innate immune system was first significantly upregulated at 2 dpi and then attenuated at 7 dpi. Toll-like receptor cascades, MyD88 cascade, phagosome pathway, cytokine signaling pathway, and lysosome pathway showed a similar expression pattern. Interestingly, we found that the ribosome pathway was significantly inhibited at 2 and 7 dpi. Gene expression regulation network enrichment analysis identified several candidate factors controlling the expression clusters. Further in vitro study showed that TGFB1 can inhibit Salmonella replication whereas TRP53 can promote Salmonella replication in porcine peripheral blood mononuclear cells and murine macrophages. These results provide new insights into the molecular mechanism of Salmonella-host interactions and clues for the genetic improvement of Salmonella infection resistance in pigs.
Pubmed ID: 30541630
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Collection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.
View all literature mentionsPublicly available database of the genes, proteins, experimentally-verified interactions and signaling pathways involved in the innate immune response of humans, mice and bovines to microbial infection. The database captures coverage of the innate immunity interactome by integrating known interactions and pathways from major public databases together with manually-curated data into a centralized resource. The database can be mined as a knowledgebase or used with the integrated bioinformatics and visualization tools for the systems level analysis of the innate immune response. Although InnateDB curation focuses on innate immunity-relevant interactions and pathways, it also incorporates detailed annotation on the entire human, mouse and bovine interactomes by integrating data (178,000+ interactions & 3,900+ pathways) from several of the major public interaction and pathway databases. InnateDB also has integrated human, mouse and bovine orthology predictions generated using Ortholgue software. Ortholgue uses a phylogenetic distance-based method to identify possible paralogs in high-throughput orthology predictions. Integrated human and mouse conserved gene order and synteny information has also been determined to provide further support for orthology predictions. InnateDB Capabilities: * View statistics for manually-curated innate immunity relevant molecular interactions. New manually curated interactions are submitted weekly. * Search for genes and proteins of interest. * Search for experimentally-verified molecular interactions by gene/protein name, interaction type, cell type, etc. * Search genes/interactions belonging to 3,900 pathways. * Visualize interactions using an intuitive subcellular localization-based layout in Cerebral. * Upload your own list of genes along with associated gene expression data (from up to 10 experimental conditions) to interactively analyze this data in a molecular interaction network context. Once you have uploaded your data, you will be able to interactively visualize interaction networks with expression data overlaid; carry out Pathway, Gene Ontology and Transcription Factor Binding Site over-representation analyses; construct orthologous interaction networks in other species; and much more. * Access curated interaction data via a dedicated PSICQUIC webservice.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsCell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus
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