Transcriptome analysis of WT and gp91-/- mice infected with Salmonella enteric server Typhimurium
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Fernanda Schreiber
PROVIDER: E-MTAB-5494 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of the genotoxins as effectors during the course of acute and chronic infections remains poorly characterized.To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine chronic infections. Immunocompetent mice were chronically infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional (MC71-TT) or an inactive (MC71-DcdtB) typhoid toxin. Keywords: salmonella typhimurium, bacterial genotoxins, typhoid toxin, chronic infection, mice model Transcriptomic analysis was performed on intestine tissues (colon, jejunum and ileum) and liver collected from 129S6/SvEvTac mice, either uninfected or infected with S. typhimurium MC71 strains (strain MC71-TT, expressing a functional typhoid toxin, and strain MC71-dcdtB, expressing an inactive typhoid toxin) for 60 days
2016-03-31 | E-GEOD-72046 | biostudies-arrayexpress
Project description:Salmonella-related infections outcome are dependent on the complex interaction between environmental factors, bacterial serotype and host genetic factors. Using ENU chemical mutagenesis, we identified a pedigree named Immunity to Typhimurium 14 (Ity14) carrying a mutation in Stat4 (c.1335+5G>A). Here we used a recognized experimental model of systemic Salmonella Typhimurium infection in mice to study the impact of Stat4 mutation on typhoid-like disease. We compare whole-genome transcriptional profiles between wild-type and Ity14 mutant mice to identify common or unique gene expression profiles between these groups.
2014-05-06 | E-MTAB-1931 | biostudies-arrayexpress
Project description:Environmental stress contributes to the outcome of infection by impacting both microbial virulence and host susceptibility to infection. Thermal processing, commonly used for decontamination of poultry in the food industry, may elicit sublethal stress on resistant serovars of Salmonella. We employed traditional heat shock temperatures (42 and 48ºC), similar to avian body temperature and poultry processing conditions, to study gene expression of Salmonella enterica serovar Typhimurium. Microarray analysis indicated that thermal shock at 42°C and 48°C induced expression of SPI-2 and SPI-5 genes, whose products are required for adhesion and survival. However, SPI-1 genes, responsible for invasion of Salmonella into host cells, were down-regulated following exposure to 42°C and 48°C. Bacterial adhesion assays showed greater adhesion of heat-stressed S. Typhimurium to Caco-2 cells compared to non-stressed bacteria. In addition, subjecting Caco-2 cells to mild heat shock (39°C), which is similar to human fever, enhanced host cell susceptibility to bacterial adhesion. Data indicate that thermal stress enhances bacterial colonization and host cell susceptibility to adhesion during S. Typhimurium infection.
2009-12-25 | GSE18089 | GEO
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.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
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
CC0
Public Domain Dedication for more information.
2015-07-30 | MODEL1507180058 | BioModels
Project description:Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of the genotoxins as effectors during the course of acute and chronic infections remains poorly characterized.To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine chronic infections. Immunocompetent mice were chronically infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional (MC71-TT) or an inactive (MC71-DcdtB) typhoid toxin. Keywords: salmonella typhimurium, bacterial genotoxins, typhoid toxin, chronic infection, mice model
2016-03-31 | GSE72046 | GEO
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
Project description:Transcriptional profiling of the zebrafish embryonic host response to a systemic bacterial infection with Salmonella typhimurium (strain SL1027); comparison between traf6 knock-down and control morpholino treated embryos. Two-way factorial dual colour design with factor 1 'infection with Salmonella enterica serovar Typhimurium (S. typhimurium)' and factor 2 'morpholino knock-down of traf6' using a common reference made from the sample pool. All infection experiments were performed using mixed egg clutches of ABxTL strain zebrafish. Embryos injected with traf6 morpholino or a 5bp mismatch control morpholino were staged at 27 hours post fertilization (hpf) by morphological criteria and approximately 250 cfu of DsRed expressing Salmonella bacteria were injected into the caudal vein close to the urogenital opening. As a control an equal volume of PBS was likewise injected. Pools of 20-40 infected and control embryos were collected 8 hours post infection (hpi). For the microarray analysis, the whole procedure was preformed in triplicate on separate days. The triplicates are marked 1,2 and 3.
2010-08-01 | E-GEOD-20310 | biostudies-arrayexpress
Project description:Single-cell RNA-seq from CD4+ T lymphocytes from uninfected steady-state mouse, two mice with Salmonella typhimurium infection at day 14 and one mouse at day 49 post-infection. Used to demonstrate application of reconstruction and analysis of T cell receptor sequences from single-cell RNA-seq.
2016-03-06 | E-MTAB-3857 | biostudies-arrayexpress
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:MicroRNAs have well-established roles in eukaryotic host responses to viruses and extracellular bacterial pathogens. In contrast, microRNA responses to invasive bacteria have remained unknown. Here, we report cell type-dependent microRNA regulations upon infection of mammalian cells with the enteroinvasive pathogen, Salmonella Typhimurium. Murine macrophages strongly up-regulate NF-κB associated microRNAs; strikingly, these regulations which are induced by the bacterial lipopolysaccharides (LPS) occur and persist regardless of successful host invasion and/or replication, or whether an inflammatory response is mounted, suggesting that microRNAs belong to the first line of anti-bacterial defence. However, a suppression of the global immune regulator miR-155 in endotoxintolerant macrophages revealed that microRNA responses also depend on the status of infected cells. This study identifies the let-7 family as the common denominator of Salmonella regulated microRNAs in macrophages and epithelial cells, and suggests that repression of let-7 relieves cytokine IL-6 and IL-10 mRNAs from negative post-transcriptional control. Our results establish a paradigm of microRNA-mediated feed-forward activation of inflammatory factors when mammalian cells are targeted by bacterial pathogens. The murine macrophage cell-line RAW 264.7 was exposed to wild-type Salmonella typhimurium SL1344 or to the corresponding knockout strain lacking both major genomic loci associated with Salmonella pathogenicity ("SPI1" and "SPI2"). To induce infectivity overnight cultures of Salmonella were dilluted 1:100 and grown to OD2. Host cells at a density of approximately 10e6 per well of a 6-well plate were infected at an MOI of 1. Upon initial incubation for 30 min cells were further incubated for 24 h in RPMI supplemented with gentamicin (10 µg / ml). As determined by a gentamicin protection and plating assay the SPI1/2 double knockout strain is deficient in both invasion and intracellular replication. We compared mouse mRNA abundances between cells infected with wild-type ("24WT") or SPI1/2 knockout Salmonella ("24SPI1/2") and non-infected, mock-treated controls ("24C"). Both strains mounted a similar inflammatory response as judged from the abundance of pro-inflammatory genes compared to the controls. These data indicate, that macrophages can mount a full inflammatory response to extracellular bacteria, that is not further enhanced or attenuated by the sensing of intracellular bacteria. Murine RAW 264.7 cells were rendered endotoxin-tolerant by pre-exposure to heat-killed Salmonella typhimurium SL1344 ("HKS") at an MOI of 10 for 20 h. 5 days upon removal of the HKS stimulus cells were exposed to wild-type Salmonella typhimurium SL1344 or to the corresponding knockout strain lacking both major genomic loci associated with Salmonella pathogenicity ("SPI1" and "SPI2"). To induce infectivity overnight cultures of Salmonella were dilluted 1:100 and grown to OD2. Host cells at a density of approximately 10e6 per well of a 6-well plate were infected at an MOI of 1. Upon initial incubation for 30 min cells were further incubated for 24 h in RPMI supplemented with gentamicin (10 µg / ml). As determined by a gentamicin protection and plating assay the SPI1/2 double knockout strain is deficient in both invasion and intracellular replication. The wild-type Salmonella strain invades and replicates in endotoxin-tolerant RAW 264.7 cells, though the intracellular replication rate is significantly reduced (by roughly 40 %) compared to naive RAW 264.7 cells. We compared mouse mRNA abundances between cells infected with wild-type ("wt") and non-infected, mock-treated controls ("Mock") or between wild-type ("wt") and SPI1/2-knockout ("SPI1/2") infected cells. As apparent from the Microarray data the wild-type Salmonella strain induces a typical inflamatory response in endotoxin-tolerant RAW 264.7 cells (as judged from the fold-induction of NFkB-inducible genes). As expected however, mRNAs corresponding to known inflammatory genes are significantly less abundant in response to the non-invasive SPI1/2 knockout strain, compared to wild-type infection. These data indicate, that endotoxin-tolerance renders macrophages largely insensitive to extracellular, but not to intracellular bacteria. ***This submission represents the mRNA component of the study
2011-03-10 | E-GEOD-27703 | biostudies-arrayexpress