Analysis by High Density cDNA Arrays of Altered Gene Expression in Human Intestinal Epithelial Cells in Response to Infection with the Invasive Enteric BacteriaSalmonella

Abstract

Many clinically important enteric pathogens initiate disease by invading and passing through the intestinal epithelium, a process accompanied by increased epithelial expression of proinflammatory cytokines. To further define the role intestinal epithelial cells play in initiating and modulating the host response to infection with invasive bacteria, hybrid selection on high density cDNA arrays was used to characterize the mRNA expression profile of ϳ4,300 genes in human intestinal epithelial cells after infection with the prototypic invasive bacteria, Salmonella. Selected findings were further evaluated by reverse transcription-polymerase chain reaction, Northern blot analysis, and protein assays. Epithelial infection with Salmonella significantly up-regulated mRNA expression of a relatively small fraction of all genes tested. Of these, several cytokines (granulocyte colony-stimulating factor, inhibin A, Epstein-Barr virusinduced gene 3, interleukin-8, macrophage inflammatory protein-2␣), kinases (TKT, Eck, HEK), transcription factors (interferon regulatory factor-1), and HLA class I were the most prominent. Furthermore, the transcription factor NF-B is shown to be important for inducible mRNA expression for a broad group of genes tested. These findings expand the repertoire of known epithelial cell responses to infection with an invasive enteric pathogen. The results also show that evaluation of mRNA expression profiles by cDNA array analysis is a powerful approach to characterizing and understanding host-pathogen interactions.

Probiotic bacteria change Escherichia coli-induced gene expression in cultured colonocytes: Implications in intestinal pathophysiology

“…In the event of specific infections, epithelial cells express and secrete proinflammatory and chemoattractant cytokines [48] that further transmit signals to the underlying cells in the reticuloendothelial system [47] . The virulence factors and the host responses to these factors in various diseases have been studied in a fair amount of detail (E. coli, Vibrio cholerae, Salmonella and Pseudomonas) using tissue culture and in vivo models, and specific genes and gene functions have been described [49][50][51][52] . These experiments have utilized single bacterial strains.…”

Immediate/Early Response to Trypanosoma cruzi Infection Involves Minimal Modulation of Host Cell Transcription

“…In addition, the most highly represented group of genes induced by T. cruzi, the ISGs, were not induced by T. gondii, bacteria, or fungal pathogens (9, 10, 13, 14). One exception was IRF-1, which was not induced by T. cruzi but was up-regulated in response to T. gondii (14), Pseudomonas (11), and Salmo- nella (10) in the absence of induction of other ISGs. Although relatively rapid modulation of ISG transcription was observed in virus-infected cells (3,4,6), similarity in host response to T. cruzi and these viral pathogens does not extend beyond this set of genes.…”

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

“…Another study that investigated the response of U-937 human monocytes to S. enterica serovar Typhimurium infection and the role of PhoP in this response detected upregulation of IL-8, MIP-1α, MIP-1β, IL23p19, and IκBα [118]. Genes upregulated in the human intestinal epithelial cell line HT-29 infected with S. enterica serovar Dublin for 3, 8, or 20 h, included several cytokines (G-CSF, Inhibin βA, EBI3, MIP-2α, IL-8), kinases (TKT, Eck, HEK), transcription factors (IRF-1), and HLA class I [119]. Other interesting examples of global in vitro and in vivo studies are the gene expression profiling in chicken heterophils infected with S. enterica serovar Enteritidis [120], the analysis of transcriptional responses to S. enterica serovar Choleraesuis infections in pig mesenteric lymph nodes [121], the analysis of the gene expression response of the rat small intestine following oral infection with S. enterica serovar Enteritidis [122], and the transcriptional profiles from S. enterica serovar Typhi-infected children [123].…”