Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited therapeutic options. The diversity and composition of intra-tumoral microbiota are associated with PDAC outcomes, and modulating the tumor microbiota has the potential to influence tumor growth and host-immune response. Here, we explore whether intervention with butyrate-producing probiotic can limit PDAC progression. By analyzing TCGA (PAAD) dataset, we found that tumoral butyrate-producing microbiota links to better prognosis and less aggressive features of PDAC. Intervention with Clostridium butyricum or its metabolite butyrate triggered superoxidative stress and intracellular lipid accumulation, which enhanced ferroptosis susceptibility of PDAC. Our study reveals a novel antitumor mechanism of butyrate, and suggests the therapeutic potential of butyrate-producing probiotics in PDAC.
Project description:This SuperSeries is composed of the following subset Series: GSE25468: Expression data from Human foreskin fibroblasts (HFFs) infected with Toxoplasma gondii. GSE25469: Expression data from WT or p65-/- mouse embryonic fibroblasts (MEFs) infected with Toxoplasma gondii. Refer to individual Series
Project description:The closely related protozoan parasites Toxoplasma gondii and Neospora caninum display similar life cycles, subcellular ultrastructure, invasion mechanisms, metabolic pathways, and genome organization, but differ in their host range and disease pathogenesis. Type II (?) interferon has long been known to be the major mediator of innate and adaptive immunity to Toxoplasma infection, but genome-wide expression profiling of infected host cells indicates that Neospora is a potent activator of the type I (?/?) interferon pathways typically associated with antiviral responses. Infection of macrophages from mice with targeted deletions in various innate sensing genes demonstrates that host responses to Neospora are dependent on the toll-like receptor Tlr3 and the adapter protein Trif. Consistent with this observation, RNA from Neospora elicits type I interferon responses when targeted to the host endo-lysosomal system. While live Toxoplasma fails to induce type I interferon, heat-killed parasites do trigger this response, and co-infection studies reveal that T. gondii actively suppresses the production of type I interferon. These findings reveal that eukaryotic pathogens can be potent inducers of type I interferon and that some parasite species, like Toxoplasma gondii, have evolved mechanisms to suppress this response. In vitro cultures of bone marrow-derived macrophages from WT or IFNAR2-/- mice were infected with either Toxoplasma gondii (VEG strain) or Neospora caninum (Nc2 strain) for 17 hours. RNA was collected from biological replicates for expression profiling by microarray. Uninfected controls for both WT and IFNAR2-/- were used as a reference.
Project description:Analysis of Ly6Chi monocytes from small intestine lamina propria (SILP) and blood of day 8 Toxoplasma gondii infected mice at gene expression level. The hypothesis tested in the present study was that Ly6Chi monocytes from SILP have altered expression of regulatory factors to blood monocytes. Results provide important information on the regulatory to effector balance of genes expressed by Ly6Chi monocytes during an acute inflammatory response. Ly6Chi inflammatory monocytes were sorted by FACS from the blood or small intestine lamina propria (SILP) of Toxoplasma gondii infected C57BL/6 mice. Cells were isolated at day 8 after infection and total RNA obtained from sorted populations. Three biological replicates were acquired for both blood and SILP from pooled animals.
Project description:The outcome of infections with Toxoplasma gondii in humans is dependent in part on the genetic makeup of the infecting organism. Recent studies have indicated that most infecting Toxoplasma organisms fall into 1 of 3 canonical lineages. Previous studies have investigated the effects of Toxoplasma on its host cell transcriptome. Little is known, however, about the effects of three canonical lineages on brain cells, the principal site of parasite lifelong persistence. In this study, we examined the transcriptional profile of human neuroepithelioma cells in response to T. gondii infection using microarray analysis to characterize the strain-specific host cell response to 3 canonical T. gondii strains. We found that the extent of the expression changes varied considerably among the three strains. Neuroepithelial cells infected with type I exhibited the most differential gene expression, whereas type II infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to central nervous system while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter expression of a clearly defined set of genes. Moreover, Ingenuity pathway analysis (IPA) revealed the sophistication of different strain in its interactions with the host. These differences may explain some of the variation in the neurobiological effects of different strains of Toxoplasma on infected individuals. We infected SK-N-MC cells with 3 canonical Toxoplasma strains and assessed their gene expression in RNA at 20 hours post-infection using Affymetrix GeneChip. Infections and controls (no tachyzoites) were performed in duplicate and experiments for each strain were carried out on three separate occasions in order to include both technical replicates and biological replicates.
Project description:Toxoplasma gondii is an apicomplexan parasite infecting human and animals, causing huge health concerns and economic losses. However, it is unclear about the exact mechanism of T.gondii tachyzoite infected macrophage and macrophage resisted T.gondii, especially for local isolates such as TgHB1 isolated in China. Our study focused on the transcriptional difference of pig alveolar macrophages (3D4/21) infected with china isolated TgHB1 compared to TgRH and TgME49 toxoplasma gondii standard strains.
Project description:The goal of this study was to identify the neural systems that underlie the behavorial changes in intermediate hosts of Toxoplasma gondii. Using a mouse whole genome microarray, we analyzed gene expression in the frontal cortex during the latent stages of infection. We found marked sex-dependent effects on gene transcription in mice. In female mice, Toxoplasma infection altered the expression of genes involved in the development of the forebrain, neurogenesis, sensory and motor coordination. In male mice, infection led mainly to modulation of genes associated with olfaction. Our results indicate that the gender of the host plays a major role in determining variable brain changes following Toxoplasma infection. Male and female BALB/c mice (infected female: n=5; infected male: n=5; female control: n=5; male control: n=4) were used in this study. They were sacrificed approximately 6 month post infection and the frontal cortices harvested. RNA transcript levels were quantified by microarray analyses using Illumina Mouse Ref-8 v2.0 Expression BeadChips.
Project description:Expression profile microarray of human foreskin fibroblast cell comparing control untreated HFF cell with HFF cell infected with ME49 strain.Study on Toxoplasma gondii infection of HFF cell LncRNAs expression, for further studies on the differential exprssion of LncRNAs in HFF cell against the infection of Toxoplasma gondii research provide the basic function.