PARP1 and Salmonella
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE19174 | GEO | 2010/05/01
SECONDARY ACCESSION(S): PRJNA120589
REPOSITORIES: GEO
Similar Datasets
Project description:BACKGROUND & AIMS: The immune system comprises an innate and an adaptive immune response to combat pathogenic agents. The human enteropathogen Salmonella enterica serovar Typhimurium invades the intestinal mucosa and triggers an early innate pro-inflammatory host gene response, which results in diarrheal disease. Several host factors are involved in the acute early response to Salmonella infection. Transcription factors and transcription co-regulators have an especially important function, because they are required for the expression and synthesis of pro-inflammatory cytokines, chemokines and adhesion molecules. A central transcription factor involved in inflammation is NF-κB, which requires the nuclear protein PARP1 as co-factor for the expression of some of its target genes. Here, we investigated the role of PARP1 during Salmonella infection using a mouse model for Salmonella-induced colitis. METHODS: To study enterocolitis by Salmonella Typhimurium, an established mouse model system, which relies on streptomycin-pretreatment prior to Salmonella infection, was employed. Histopathologic signs of inflammation and cecum colonization at various time-points after infection of wild type and PARP1 knockout mice were analyzed. PARP1 expression in the gut mucosa was studied by quantitative RT-PCR, Western blot and immunofluorescence. Gene expression profiles of infected and control infected mice in the wild type or PARP1 knockout background were obtained by whole mouse genome arrays and confirmed by quantitative RT-PCR. 2 genotypes (wildtype, PARP1 knockout), 2 treatments (Salmonella SB300 infection, Salmonella SB161 control infection), 2 time-points (6h, 10h). 2-3 replicates/condition.
2010-05-27 | E-GEOD-19174 | biostudies-arrayexpress
Project description:gd T cells have an important yet incompletely defined role in inflammation associated with a variety of infectious and autoimmune conditions. To better understand the precise roles of gd T cells relative to ab T cells in a specific infection, we utilized Salmonella Enterica Serovar Typhimurium (S. typhimurium) infection in cattle as it is a leading cause of disease in cattle and closely approximates S. typhimurium-induced enterocolitis in humans. To best represent phenotype and gene expression changes occurring in the gut mucosa early in S. typhimurium infection, gd and ab T cells were collected directly from the mesenteric lymphatic ducts and analyzed by FACS or immediately sorted and processed for microarray analysis. Gene expression profiles were compared at intervals during infection within T cell subsets. The majority of gene expression changes in both subsets occurred 48 hours after infection. In response to S. typhimurium infection there was an increase in expression of several genes in gd T cells which were indicative of activation, proliferation and innate function, whereas in ab T cells gene expression changes suggested a lack of S. typhimurium-specific response. This work represents the first focus on gene expression trends in tissue-derived T lymphocytes in an in vivo model that is highly relevant to human S. typhimurium-induced enterocolitis. Keywords: Comparison of ab and gd T cells in bovine lymphatic fluid time course after salmonella or mock infection
2007-06-30 | GSE3439 | GEO
Project description:Regulation of the immune response to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection is a complex process, influenced by the interaction between genetic and environmental factors. Different inbred strains of mice exhibit distinct levels of resistance to S. Typhimurium infection, ranging from susceptible (e.g., C57BL/6J) to resistant (e.g., DBA/2J) strains. However, the underlying molecular mechanisms contributing to the host response remain elusive. In this study, we present a comprehensive proteomics profiling of spleen tissues from C57BL/6J and DBA/2J strains with different doses of S. Typhimurium infection by tandem tag mass coupled with two-dimensional liquid chromatography-tandem mass spectrometry (TMT-LC/LC-MS/MS). We identified and quantified 3,986 proteins, resulting in 475 differentially expressed proteins (DEPs) between C57BL/6J and DBA/2J strains. Functional enrichment analysis unveiled that the mechanism of innate immune responses to S. Typhimurium infection could be associated with several signaling pathways, including the interferon signaling pathway. We experimentally validated the roles of interferon signaling pathway in innate immune response to S. Typhimurium infection using IFN-γ neutralization assay. We further illustrated the roles of macrophage cells and pro-inflammatory cytokines in the mechanisms underlying the resistance to S. Typhimurium using qRT-PCR. Taken together, our results provide new insights into the genetic regulation of the immune response to S. Typhimurium infection in mice and might provide potential protein targets for controlling the infection.
2022-12-01 | PXD038436 | Pride
Project description:The GeneChip Porcine Genome Array was used to identify the transcriptional response upon Salmonella typhimurium infection in three porcine intestinal sections (jejumun, ileum and colon) along a time course of 1,2 and 6 days post infection. The objetives in this study were i) characterize transcriptional changes upon S. typhimurium infection in the intestinal mucosa; ii) identify differences among porcine intestinal sections in inmune resposes against S. typhimurium; iii) identify change that could be associated to salmonellosis pathogenesis and symtomatology; and finally, iv) identify transcriptional changes that could be induced by S. typhimurium in order to get bacterial survival and successful colonization.
2012-06-20 | GSE22596 | GEO
Project description:Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the cecum of streptomycin pre-treated mice. We determined global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. The gene expression profile was dominated by T cell derived cytokines and genes whose expression is known to be induced by these cytokines. Markedly increased mRNA levels of interferon (IFN) ï§, interleukin (IL) 22 and IL-17 were detected by quantitative real-time PCR. Furthermore, mRNA levels of genes whose expression is induced by IFNï§, IL-22 or IL-17, including macrophage inflammatory protein (MIP)-2, inducible nitric oxide synthase (iNOS), lipocalin-2, MIP-1ï¡, MIP-1ï¢, and keratinocyte-derived cytokine (KC), were also markedly increased. To assess the importance of T cells in orchestrating this pro-inflammatory gene expression profile, we depleted T cells using a monoclonal antibody prior to investigating cecal inflammation caused by serotype Typhimurium in streptomycin pre-treated mice. Depletion of CD3+ T cells resulted in a dramatic reduction in gross pathology, a significantly reduced recruitment of neutrophils and a marked reduction in mRNA levels of IFNï§, IL-22, IL-17, iNOS, lipocalin-2 and KC. Our results suggest that T cells play an important role in amplifying inflammatory responses induced by serotype Typhimurium in the cecal mucosa. Experiment Overall Design: Determine global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. For each condition, control and infected, total cecal RNA from 4 mice was pooled
2008-04-07 | E-GEOD-10594 | biostudies-arrayexpress
Project description:The GeneChip Porcine Genome Array was used to identify the transcriptional response upon Salmonella typhimurium infection in three porcine intestinal sections (jejumun, ileum and colon) along a time course of 1,2 and 6 days post infection. The objetives in this study were i) characterize transcriptional changes upon S. typhimurium infection in the intestinal mucosa; ii) identify differences among porcine intestinal sections in inmune resposes against S. typhimurium; iii) identify change that could be associated to salmonellosis pathogenesis and symtomatology; and finally, iv) identify transcriptional changes that could be induced by S. typhimurium in order to get bacterial survival and successful colonization. Sixteen male and female crossbreeds weaned piglets, approximately 4 weeks of age, were used in this study. Before infection, faecal samples from each animal were analyzed to confirm that piglets were free of Salmonella. Pigs were housed in an environmentally controlled isolation facility at 25ºC and under constant light with ad libitum access to feed and water. After an acclimation period of 5 days, pigs were challenged orally with 108 cfu of Salmonella enterica serovar Typhimurium phagetype DT104 (n=12), whereas the control group (n=4) received sterile medium orally. The four non-infected control pigs were necropsied two hours prior to experimental infection. Four randomly chosen infected pigs were necropsied at 1 day post infection (dpi), 2 dpi and 6 dpi, respectively. Faecal swabs, blood and tissues samples were aseptically collected. Ileum was collected, sectioned in pieces of around 10 cm and immediately frozen in liquid nitrogen for mucosa isolation and RNA purification. To ensure the inoculated pigs were infected, faecal samples were cultured and checked for positive Salmonellae organism Four reps per treatment and tissue group except 'Ileum 1dpi' has only 3 replicates.
2012-06-19 | E-GEOD-22596 | biostudies-arrayexpress
Project description:Raghunathan2009 - Genome-scale metabolic
network of Salmonella typhimurium (iRR1083)
This model is described in the article:
Constraint-based analysis of
metabolic capacity of Salmonella typhimurium during
host-pathogen interaction.
Raghunathan A, Reed J, Shin S,
Palsson B, Daefler S.
BMC Syst Biol 2009; 3: 38
Abstract:
BACKGROUND: Infections with Salmonella cause significant
morbidity and mortality worldwide. Replication of Salmonella
typhimurium inside its host cell is a model system for studying
the pathogenesis of intracellular bacterial infections.
Genome-scale modeling of bacterial metabolic networks provides
a powerful tool to identify and analyze pathways required for
successful intracellular replication during host-pathogen
interaction. RESULTS: We have developed and validated a
genome-scale metabolic network of Salmonella typhimurium LT2
(iRR1083). This model accounts for 1,083 genes that encode
proteins catalyzing 1,087 unique metabolic and transport
reactions in the bacterium. We employed flux balance analysis
and in silico gene essentiality analysis to investigate growth
under a wide range of conditions that mimic in vitro and host
cell environments. Gene expression profiling of S. typhimurium
isolated from macrophage cell lines was used to constrain the
model to predict metabolic pathways that are likely to be
operational during infection. CONCLUSION: Our analysis suggests
that there is a robust minimal set of metabolic pathways that
is required for successful replication of Salmonella inside the
host cell. This model also serves as platform for the
integration of high-throughput data. Its computational power
allows identification of networked metabolic pathways and
generation of hypotheses about metabolism during infection,
which might be used for the rational design of novel
antibiotics or vaccine strains.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180058.
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To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
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Public Domain Dedication for more information.
2015-07-30 | MODEL1507180058 | BioModels
Project description:Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis in humans and calves characterized by diarrhea and polymorphonuclear cell (PMN) influx to the intestinal mucosa. The Salmonella Type III Secretion System encoded at Pathogenicity Island I (SPI-1) translocates the Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into the host epithelial cell cytoplasm. These five effector proteins act in concert to induce fluid secretion and transcription of C-X-C chemokines, which serve to recruit PMNs to the intestine. While the individual molecular interactions of these Salmonella proteins with cultured host cells have been extensively characterized, their combined role in the generation of fluid secretion and inflammation is less well understood. A bovine ligated ileal loop model was used in conjunction with a custom bovine microarray to determine intestinal response to acute S. Typhimurium infection in the calf. Gene expression responses to both wild type S. Typhimurium a delta sipA, sopABDE2 mutant were measured at seven times during the initial 12 hours of infection. Microarray analysis confirmed increased expression of genes encoding proteins previously associated with immune response to Salmonella spp. infection. Gene expression changes were mapped to molecular interaction pathways and changes in expression of mechanistic genes, which are defined as perturbed genes identified by Bayesian genetic network modeling, were strongly involved in the mechanisms of the host immune response. In addition to correctly identifying known effects of wild type S. Typhimurium on host (bovine) gene expression, Bayesian genetic network modeling identified novel effects of S. Typhimurium on several molecular interaction pathways. Novel effects impacted gene regulation in the following pathways: adipocytokine signaling, insulin signaling, complement and coagulation cascades, axon guidance, gap junction, neuroactive ligand-receptor interaction, long-term depression, long-term potentiation, melanogenesis, and natural killer cell mediated cytotoxicity. Known effects were observed in the following pathways: regulation of actin cytoskeleton, apoptosis, cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), MAPK signaling, calcium signaling, Jak-STAT signaling, leukocyte transendothelial migration, adherens junction, tight junction, and ECM-receptor interactions, phosphatidylinositol signaling system, and antigen processing and presentation. Quantitative real-time PCR was used to verify the expression of some of these mechanistic genes.
2012-01-10 | GSE13847 | GEO
Project description:Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis in humans and calves characterized by diarrhea and polymorphonuclear cell (PMN) influx to the intestinal mucosa. The Salmonella Type III Secretion System encoded at Pathogenicity Island I (SPI-1) translocates the Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into the host epithelial cell cytoplasm. These five effector proteins act in concert to induce fluid secretion and transcription of C-X-C chemokines, which serve to recruit PMNs to the intestine. While the individual molecular interactions of these Salmonella proteins with cultured host cells have been extensively characterized, their combined role in the generation of fluid secretion and inflammation is less well understood. A bovine ligated ileal loop model was used in conjunction with a custom bovine microarray to determine intestinal response to acute S. Typhimurium infection in the calf. Gene expression responses to both wild type S. Typhimurium a delta sipA, sopABDE2 mutant were measured at seven times during the initial 12 hours of infection. Microarray analysis confirmed increased expression of genes encoding proteins previously associated with immune response to Salmonella spp. infection. Gene expression changes were mapped to molecular interaction pathways and changes in expression of mechanistic genes, which are defined as perturbed genes identified by Bayesian genetic network modeling, were strongly involved in the mechanisms of the host immune response. In addition to correctly identifying known effects of wild type S. Typhimurium on host (bovine) gene expression, Bayesian genetic network modeling identified novel effects of S. Typhimurium on several molecular interaction pathways. Novel effects impacted gene regulation in the following pathways: adipocytokine signaling, insulin signaling, complement and coagulation cascades, axon guidance, gap junction, neuroactive ligand-receptor interaction, long-term depression, long-term potentiation, melanogenesis, and natural killer cell mediated cytotoxicity. Known effects were observed in the following pathways: regulation of actin cytoskeleton, apoptosis, cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), MAPK signaling, calcium signaling, Jak-STAT signaling, leukocyte transendothelial migration, adherens junction, tight junction, and ECM-receptor interactions, phosphatidylinositol signaling system, and antigen processing and presentation. Quantitative real-time PCR was used to verify the expression of some of these mechanistic genes. Microarrays were used to examine the transcriptional profiles of bovine intestinal epithelia infected with wild type Salmonella enterica serotype Typhimurium (control and wild type or delta sipA sopABDE2 mutant infected) across seven time points (15 min, 30 min, 1, 2, 4, 8, and 12 hours). Experiments were performed in quadruplicate (bovine ligated ileal loops surgeries were performed with four calves), generateing a total of 84 arrays.
2012-01-10 | E-GEOD-13847 | biostudies-arrayexpress
Project description:Group 3 innate lymphoid cells (ILC3s) produce interleukin (IL)-22 and, together with other cells in the gut, orchestrate to mount productive host immunity against bacterial infection. However, the role of ILC3s in Salmonella enterica serovar Typhimurium (S. Typhimurium) infection, which causes foodborne enteritis in humans, remains elusive. Here, we show that S. Typhimurium exploit ILC3-produced IL-22 to promote its infection. Specifically, S. Typhimurium secrete flagellin through activation of the TLR5-Myd88-IL-23 signaling pathway in antigen presenting cells (APCs) to selectively enhance IL-22 production by ILC3s, but not T cells. Deletion of ILC3s but not T cells in mice led to better control of S. Typhimurium infection. We also show that S. Typhimurium can invade ILC3s directly and cause caspase-1-mediated ILC3 pyroptosis independently of flagellin. Genetic ablation of Casp1 in mice leads to increased ILC3 survival and IL-22 production, and enhanced S. Typhimurium infection. Collectively, our data suggest a key host defense mechanism against S. Typhimurium infection via induction of ILC3 death to limit intracellular bacteria and reduce IL-22 production.
2022-05-23 | GSE201292 | GEO