Combined transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions
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ABSTRACT:
PROVIDER: PRJNA326689 | ENA |
REPOSITORIES: ENA
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Project description:The opportunistic fungal pathogen Candida albicans is a common cause of life-threatening nosocomial bloodstream infections. In the murine model of systemic candidiasis the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To get a better understanding of the organ-specific differences in host-pathogen interaction during systemic murine candidiasis, we performed a time-course gene expression profiling to investigate the differential responses of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We clearly demonstrate a delayed immune response on the transcriptional level in kidney accompanied by late induction of fungal stress response genes in this organ. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptional profile resembling that of phagocytosed cells, suggesting that the resident phagocytic system contributes significantly to fungal control in the liver. Although no visible filamentation occurred in the liver, C. albicans hypha-associated genes were upregulated, indicating an uncoupling of gene expression and morphology during infection of this organ. In vitro the induction of hypha-associated gene expression in yeast cells led to altered interaction with macrophages, suggesting that the observed transcriptional changes affect host-pathogen interaction in vivo. Consistently, the combination of host and pathogen transcriptional data in an inference network model implied that C. albicans cell wall remodeling and metabolism were connected to the immune responses in kidney and liver. Furthermore, the network suggested links between fungal iron acquisition and amino acid metabolism in the kidney and host organ homeostasis. Thus, this work provides novel insights into the organ-specific host-pathogen interactions during systemic C. albicans infection.
2016-11-18 | GSE83679 | GEO
Project description:The opportunistic fungal pathogen Candida albicans is a common cause of life-threatening nosocomial bloodstream infections. In the murine model of systemic candidiasis the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To get a better understanding of the organ-specific differences in host-pathogen interaction during systemic murine candidiasis, we performed a time-course gene expression profiling to investigate the differential responses of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We clearly demonstrate a delayed immune response on the transcriptional level in kidney accompanied by late induction of fungal stress response genes in this organ. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptional profile resembling that of phagocytosed cells, suggesting that the resident phagocytic system contributes significantly to fungal control in the liver. Although no visible filamentation occurred in the liver, C. albicans hypha-associated genes were upregulated, indicating an uncoupling of gene expression and morphology during infection of this organ. In vitro the induction of hypha-associated gene expression in yeast cells led to altered interaction with macrophages, suggesting that the observed transcriptional changes affect host-pathogen interaction in vivo. Consistently, the combination of host and pathogen transcriptional data in an inference network model implied that C. albicans cell wall remodeling and metabolism were connected to the immune responses in kidney and liver. Furthermore, the network suggested links between fungal iron acquisition and amino acid metabolism in the kidney and host organ homeostasis. Thus, this work provides novel insights into the organ-specific host-pathogen interactions during systemic C. albicans infection.
2016-11-18 | GSE83681 | GEO
Project description:The opportunistic fungal pathogen Candida albicans is a common cause of life-threatening nosocomial bloodstream infections. In the murine model of systemic candidiasis the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To get a better understanding of the organ-specific differences in host-pathogen interaction during systemic murine candidiasis, we performed a time-course gene expression profiling to investigate the differential responses of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We clearly demonstrate a delayed immune response on the transcriptional level in kidney accompanied by late induction of fungal stress response genes in this organ. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptional profile resembling that of phagocytosed cells, suggesting that the resident phagocytic system contributes significantly to fungal control in the liver. Although no visible filamentation occurred in the liver, C. albicans hypha-associated genes were upregulated, indicating an uncoupling of gene expression and morphology during infection of this organ. In vitro the induction of hypha-associated gene expression in yeast cells led to altered interaction with macrophages, suggesting that the observed transcriptional changes affect host-pathogen interaction in vivo. Consistently, the combination of host and pathogen transcriptional data in an inference network model implied that C. albicans cell wall remodeling and metabolism were connected to the immune responses in kidney and liver. Furthermore, the network suggested links between fungal iron acquisition and amino acid metabolism in the kidney and host organ homeostasis. Thus, this work provides novel insights into the organ-specific host-pathogen interactions during systemic C. albicans infection.
2016-11-18 | GSE83680 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-11-18 | GSE83682 | GEO
Project description: Not available
| S-EPMC5093689 | biostudies-literature
Project description:Candida species is a common fungus that had evolved as both commensal and opportunistic pathogen in humans. The rise in human morbidity and mortality caused by Candida species sparked an alarming concern. However, the thin line between commensalism and infection as well as the analysis of Candida host-pathogen interactions has not been completely elucidated prior to the birth of global gene expression technologies. Gene expression analysis of host response upon systemic candidiasis had been carried out using Beadarray and validated by using GenomeLab™ GeXP multiplex PCR. Whole blood from infected mouse was isolated, globin mRNA depleted through subtractive hybridization and its RNA purified. Results from microarray data demonstrated increased expression of genes involved in the pathogen recognition, signal transduction, inflammation, microbial killing and in antigen processing. Interestingly, we also discovered possible increment of erythropoiesis in our animal model and this lead us to believe that Candida tropicalis might possess potent haemolytic factors to sequester iron from the host erythrocytes. Taken together, our data also suggest novel genes such as syndecans and dendritic cell immunoreceptor which might be exploited by Candida tropicalis in its pathogenesis in the host. Nevertheless, the challenge ahead is to understand the specific roles of these genes that underlies in Candida tropicalis pathogenesis. For gene expression analysis, BALB/c mice (six-week-old female weighing 20-25g) were used and the animals were randomized, assigned to the control, sublethal infection and lethal infection groups. At the time of killing, mice were anesthetized and exsanguinated by cardiac puncture. Approximately 200 µl of whole blood was collected and added into 2 ml tubes preloaded with RNAlater (Sigma-Aldrich CO, USA) and stored in -80 °C.
2010-12-31 | E-GEOD-16339 | biostudies-arrayexpress
Project description:Candida species is a common fungus that had evolved as both commensal and opportunistic pathogen in humans. The rise in human morbidity and mortality caused by Candida species sparked an alarming concern. However, the thin line between commensalism and infection as well as the analysis of Candida host-pathogen interactions has not been completely elucidated prior to the birth of global gene expression technologies. Gene expression analysis of host response upon systemic candidiasis had been carried out using Beadarray and validated by using GenomeLab™ GeXP multiplex PCR. Whole blood from infected mouse was isolated, globin mRNA depleted through subtractive hybridization and its RNA purified. Results from microarray data demonstrated increased expression of genes involved in the pathogen recognition, signal transduction, inflammation, microbial killing and in antigen processing. Interestingly, we also discovered possible increment of erythropoiesis in our animal model and this lead us to believe that Candida tropicalis might possess potent haemolytic factors to sequester iron from the host erythrocytes. Taken together, our data also suggest novel genes such as syndecans and dendritic cell immunoreceptor which might be exploited by Candida tropicalis in its pathogenesis in the host. Nevertheless, the challenge ahead is to understand the specific roles of these genes that underlies in Candida tropicalis pathogenesis.
2010-12-31 | GSE16339 | GEO
Project description:Combined transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions [C. albicans]
| PRJNA326692 | ENA
Project description:Combined transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions [mouse tissues 8 h]
| PRJNA326711 | ENA
Project description:Combined transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions [mouse tissues 12,24,72 h]
| PRJNA326710 | ENA