Abstract
BackgroundAcute enteritis caused by Salmonella is a public health concern. Salmonella infection is also known to increase the risk of inflammatory bowel diseases and cancer. Therefore, it is important to understand how Salmonella works in targeting eukaryotic pathways in intestinal infection. However, the global physiological function of Salmonella typhimurium in intestinal mucosa in vivo is unclear. In this study, a whole genome approach combined with bioinformatics assays was used to investigate the in vivo genetic responses of the mouse colon to Salmonella. We focused on the intestinal responses in the early stage (8 hours) and late stage (4 days) after Salmonella infection.ResultsOf the 28,000 genes represented on the array, our analysis of mRNA expression in mouse colon mucosa showed that a total of 856 genes were expressed differentially at 8 hours post-infection. At 4 days post-infection, a total of 7558 genes were expressed differentially. 23 differentially expressed genes from the microarray data was further examined by real-time PCR. Ingenuity Pathways Analysis identified that the most significant pathway associated with the differentially expressed genes in 8 hours post-infection is oxidative phosphorylation, which targets the mitochondria. At the late stage of infection, a series of pathways associated with immune and inflammatory response, proliferation, and apoptosis were identified, whereas the oxidative phosphorylation was shut off. Histology analysis confirmed the biological role of Salmonella, which induced a physiological state of inflammation and proliferation in the colon mucosa through the regulation of multiple signaling pathways. Most of the metabolism-related pathways were targeted by down-regulated genes, and a general repression process of metabolic pathways was observed. Network analysis supported IFN-γ and TNF-α function as mediators of the immune/inflammatory response for host defense against pathogen.ConclusionOur study provides novel genome-wide transcriptional profiling data on the mouse colon mucosa's response to the Salmonella typhimurium infection. Building the pathways and networks of interactions between these genes help us to understand the complex interplay in the mice colon during Salmonella infection, and further provide new insights into the molecular cascade, which is mobilized to combat Salmonella-associated colon infection in vivo.
Highlights
Acute enteritis caused by Salmonella is a public health concern
Global gene differential expression during the time course of Salmonella infection in the mouse colon mucosa In this current study, we focused on the mouse colon mucosa’s responses to Salmonella infection at both 8 hours and 4 days post infection in vivo
Previous studies indicate that the 8 hours post-infection provides insights into the early events of Salmonella infection in the colon, whereas investigation of the gene expression response at 4 days post-infection can show the outcome of infection and inflammation [43,44,47,48]
Summary
Salmonella infection is known to increase the risk of inflammatory bowel diseases and cancer. It is important to understand how Salmonella works in targeting eukaryotic pathways in intestinal infection. We focused on the intestinal responses in the early stage (8 hours) and late stage (4 days) after Salmonella infection. Salmonella infection can understand which pathway Salmonella target that may potentially contribute to chronic inflammation and tumorigenesis. Alive, mutated, non-invasive Salmonella has been used as a vector to target cancer cells [11]. It may be controversial if Salmonella could contribute to intestinal inflammation and cancer. It is necessary to understand the global facets of Salmonella in the intestine using animal models
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