Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Infection with bradyzoites has a diminished impact on host transcript levels relative to tachyzoite infection.

ABSTRACT: 5 arrays per condition (covering 3 biological replicate experiments) were performed on Human Foreskin Fibroblasts (HFFs) at 44 hours post infection. The four experimental conditions include uninfected "standard", uninfected "stress", tachyzoite-infected "standard+TZ", and bradyzoite-infected "stress+BZ". Bradyzoite conversion is induced at 4 hours post infection with replacement of standard DMEM+10% FCS with RPMI+1%FCS buffered with 50mM Hepes to pH 8.15. Approximately 20% of cells are infected and bradyzoite conversion is >90% in these experiments. These data are normalized using 2-D loess (span factor .4). The calculations in the manuscript are based on are log2 ratios of normalized channel 2/channel 1 medians. A development or differentiation experiment design type assays events associated with development or differentiation or moving through a life cycle. Development applies to organism(s) acquiring a mature state, and differentiation applies to cells acquiring specialized functions. Developmental Stage: Uninfected (standard or stress medium), or Tachyzoite-infected (standard medium) or Bradyzoite-infected (stress medium) Complex

ORGANISM(S): Homo sapiens

SUBMITTER: Ashley Fouts

PROVIDER: E-GEOD-8773 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Infection with Toxoplasma gondii bradyzoites has a diminished impact on host transcript levels relative to tachyzoite infection.

Fouts A E AE Boothroyd J C JC

Infection and immunity 20061106 2

Toxoplasma gondii, an intracellular pathogen, has the potential to infect nearly every warm-blooded animal but rarely causes morbidity. The ability for the parasite to convert to the bradyzoite stage and live inside slow-growing cysts that can go unnoticed by the host immune system allows for parasite persistence for the life of the infected host. This intracellular survival likely necessitates host cell modulation, and tachyzoites are known to modify a number of signaling cascades within the ho ...[more]

PMID: 17088349

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Project description:These 95 arrays are the basis for Figure 2 of our manuscript "An interferon-response induced by tumor-stroma interaction in a subset of human breast cancers". Abstract:Background Communication between different cell types is a cardinal feature of multi-cellular organisms and perturbations in these cell-cell interactions are a key feature of cancer. However, little is known about the systematic effects of cell-cell interaction on global gene expression in cancer. Methods and Findings We used an ex vivo culture model to simulate tumor-stroma interaction by systematically co-cultivating breast cancer cells with stromal fibroblasts and determined associated gene expression changes with cDNA microarrays. The picture of heterotypic interaction effects that emerged from this analysis is complex, reflecting the variation in signaling capacities and responsiveness of the involved cells. A frequent and prominent response to epithelial-mesenchymal interaction was an induction of interferon-response genes, observed in 4 of the 7 breast cancer cell lines in response to co-culture with fibroblasts, but not in normal mammary epithelial cells. In response to close contact with these breast cancer cells, the fibroblasts secreted type I interferons, which, in turn, induced expression of the IRGs in the tumor cells. Immunohistochemical analysis of human breast cancer tissues showed that STAT1, the key transcriptional activator of the interferon-response genes, and itself an IRG, was expressed in a subset of the cancers, with a striking pattern of elevated expression in the cancer cells in contact with, or close proximity to, the tumor stroma ? paralleling the response seen in our ex vivo model. In vivo, expression of the interferon-response genes was remarkably coherent, providing a basis for segregation of the 295 early-stage breast cancers into two groups. Tumors with high expression levels (n=161) of IRG were associated with significantly shorter overall survival; 59 % at 10 years versus 80% for tumors with low interferon-response gene expression levels (n=134) (log-rank p=0.001). Conclusion Our results suggest that an interaction between some breast cancer cells and stromal fibroblasts can induce an interferon response, and that this response may be associated with a greater propensity for tumor progression. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed

Project description:Patient Selection: Three hospitals were involved in the study: Dong Thap Provincial and An Giang Provincial hospitals, both located in the Mekong Delta Region of Vietnam where most of the Typhoid patients were admitted, and the Hospital for Tropical Diseases, Ho Chi Minh City, where the malarial patients were admitted. Infection status of each patient was determined by blood culture for the Typhoid patients and by microscopic examination of stained thick and thin peripheral-blood slides for the patients suspected of having Malaria. Patients with blood cultures positive for S. Typhi or S. enterica serovar Paratyphi A (S. Paratyphi A) (samples designated ST) or peripheral blood smears positive for Plasmodium falciparum or Plasmodium vivax (samples designated PF) were consented and enrolled in the study. A total of 28 S. Typhi positive patients and one S. Paratyphi A positive patient were enrolled in the first phase of the study and a further 9 S. Typhi and one S. Paratyphi A positive patient were enrolled in the second phase. Nine patients with Malaria caused by P. falciparum and one caused by P. vivax were enrolled. Sixteen uninfected healthy individuals (samples designated HC) were also enrolled in the study (one sample each). The Typhoid patients were randomly chosen to receive either Azithromycin or Gatifloxicin (20mg/kg/day for 7 days) antibiotics. Uncomplicated malaria patients were treated for 3 days with Artekin (dihydroartemisinin with piperaquine phosphate). Venous blood (2.5ml) was collected for total RNA extraction into PaxGene RNA collection tubes (Qiagen) at various times. The first sample (T1) was taken immediately on admission or entry into the study, then samples were collected, 3 (T3), 6-9 (T9 for Typhoid, T7 for Malaria), and 28-45 (T28) days following entry into the study and an average of 9 months (T9M) later. The PaxGene tubes were stored at 4degC until RNA was extracted as per the manufacturers instructions. Purified RNA was shipped on dry ice to Stanford University, CA for use in Microarray analyses. Microarrays: Experimental and reference samples (Human Universal RNA reference {Stratagene}) were amplified using the MessageAmp II aRNA Kit (Ambion) as per the manufacturer's instructions. Four micrograms amplified RNA was labeled through indirect incorporation of Cy5 (experimental) and Cy3 (reference) dyes (protocols can be found at http://cmgm.stanford.edu/pbrown/protocols/index.html). The labeled probes were then mixed and hybridized to Stanford Human cDNA arrays with 42 K features. Arrays were scanned using a Genepix 4000A laser scanner and data extracted with Genepix Pro Software version 5.1 (Axon Instruments). The data were then uploaded into the Stanford Microarray Database (SMD). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Compound Based Treatment: Drugs used for treatment Disease State: Malaria, Typhoid or Healthy Controls Keywords: disease_state_design Complex

Dataset Information

Infection with bradyzoites has a diminished impact on host transcript levels relative to tachyzoite infection.

Publications

Infection with Toxoplasma gondii bradyzoites has a diminished impact on host transcript levels relative to tachyzoite infection.

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