Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42630 | GEO | 2012/12/01
SECONDARY ACCESSION(S): PRJNA182377
REPOSITORIES: GEO
Similar Datasets
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, but human anti-fungal immunity remains poorly defined. Expression profiling of Candida-stimulated human peripheral blood mononuclear cells (PBMCs) provides new insights into Candida-specific host defense mechanisms in humans.
2014-05-01 | GSE42606 | GEO
Project description:Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections, but human anti-fungal immunity remains poorly defined. Expression profiling of Candida-stimulated human peripheral blood mononuclear cells (PBMCs) provides new insights into Candida-specific host defense mechanisms in humans. Total RNA was extracted from PBMCs from healthy human volunteers. PBMCs were stimulated with heat-killed Candida albicans (10^6/ml), non-fungal inflammatory stimuli or RPMI control for 4 or 24 hours. A large number of biological replicates (>20) were included per stimulation condition and duration.
2014-05-01 | E-GEOD-42606 | biostudies-arrayexpress
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 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. PRJNA86065 Two different strains of C. albicans (SC5314 or WO-1) were used to infect two different types of human tissue culture monolayers (HUVECs or OKF6-TERT2). RNA from the infection mixtures were harvested at 90 minutes, 5 hours and 8 hours post infection. Experiments were performed in biological duplicate.
2014-03-30 | E-GEOD-56091 | 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:Candida auris is amongst the most important emerging fungal pathogens, yet mechanistic insights in its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune cell profiling to uncover innate anti-C. auris defense mechanisms. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared to C. albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through recognition of C-type lectin receptors, mainly elicited by structurally unique C. auris mannoproteins. In in-vivo experimental models of disseminated candidiasis, C. auris was less virulent than C. albicans. Collectively, these results demonstrate that C. auris is a strong inducer of innate host defense and identify possible targets for adjuvant immunotherapy.
2020-07-23 | GSE154911 | GEO
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 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. PRJNA86065
2014-03-30 | GSE56091 | 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
2014-03-30 | GSE56092 | GEO