Mus musculus
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PROVIDER: PRJNA326710 | ENA |
REPOSITORIES: ENA
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Project description:Combined transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions
| PRJNA326689 | 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 [C. albicans]
| PRJNA326692 | ENA
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: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:Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. By integrating transcriptional analysis and functional genomics we identified Candida-specific host defense mechanisms in humans. Candida induced significant (p<10-35) expression of genes from the type I interferon (IFN) pathway in human peripheral blood mononuclear cells. This unexpectedly prominent role of type I IFN pathway in anti-Candida host defense was supported by additional evidence. Polymorphisms in type I IFN genes modulated Candida-induced cytokine production and were correlated with susceptibility to systemic candidiasis. In in-vitro experiments, type I IFNs skewed Candida-induced inflammation from a Th17-response toward a Th1-response. Patients with chronic mucocutaneaous candidiasis displayed defective expression of genes in the type I IFN pathway. These findings indicate that the type I IFN pathway is a main signature of Candida-induced inflammation and plays a crucial role in anti-Candida host defense in humans. 3 healthy controls and 2 CMC patients
2012-12-01 | E-GEOD-42630 | biostudies-arrayexpress
Project description:Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. By integrating transcriptional analysis and functional genomics we identified Candida-specific host defense mechanisms in humans. Candida induced significant (p<10-35) expression of genes from the type I interferon (IFN) pathway in human peripheral blood mononuclear cells. This unexpectedly prominent role of type I IFN pathway in anti-Candida host defense was supported by additional evidence. Polymorphisms in type I IFN genes modulated Candida-induced cytokine production and were correlated with susceptibility to systemic candidiasis. In in-vitro experiments, type I IFNs skewed Candida-induced inflammation from a Th17-response toward a Th1-response. Patients with chronic mucocutaneaous candidiasis displayed defective expression of genes in the type I IFN pathway. These findings indicate that the type I IFN pathway is a main signature of Candida-induced inflammation and plays a crucial role in anti-Candida host defense in humans.
2012-12-01 | GSE42630 | GEO
Project description:Candida albicans is the major invasive fungal pathogen of humans, causing diseases ranging from superficial mucosal infections to disseminated, systemic infections which are often life threatening. Hematogenously disseminated candidiasis (HDC) has a 47% mortality rate despite current antifungal therapy. An increase in prevalence, as well as an increasing resistance to most of the clinically important antifungal therapies, provides a strong impetus to understand the molecular mechanisms of pathogenesis and the acquisition of drug resistance. This information holds promise to identify novel therapeutic targets. A complete and accurate characterization of how the transcriptome of C. albicans responds to its interaction with cells from the host is an absolute necessity to accomplish this goal. RNA-seq (deep-sequencing of cDNA) provides an unbiased method to define comprehensively and systematically the transcriptome of an organism. We propose a comprehensive characterization of the C. albicans transcriptome in two different human tissue culture models, using RNA-seq. Such a characterization will shed unprecedented light on how fungal pathogens sense and respond to the host environment and how the host tissue responds to fungal invasion. We performed a comprehensive characterization of the C. albicans transcriptome in two different murine models of candidiasis (HDC and oropharyngeal candidiasis (OPC)), and two different human tissue culture models, using RNA-seq. Because the two murine models accurately recapitulate the pathology that is observed in clinical cases of candidiasis, we are confident that gene expression levels will provide an accurate representation of what occurs during the course of an infection in humans. Such a characterization of the in vivo transcriptome will shed unprecedented light on how fungal pathogens sense and respond to the host environment and how the host tissue responds to fungal invasion. PRJNA211732 C. albicans strain SC5314 was used to infect mice in a murine model of systemic candidiasis as well as a murine model of oropharyngeal candidiasis. For the disseminated model, kidneys were harvested at 6 hours, 12 hours, 24 hours and 48 hours after infection. For the oropharyngeal model, tongues were harvest at 1 day, 2 days, 3 days, and 5 days after infection. Total RNA was extracted from all harvested tissues and subject to RNA-seq. We also tested 3 C. albicans mutants in the disseminated model. For the infections with the mutant strains, only 1 timepoint (24 hours post-infection) was analyzed.
2014-03-30 | E-GEOD-56092 | 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