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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Differential gene expression in human myeloid dendritic cells interacting with different knockout strains of Aspergillus fumigatus in vitro

ABSTRACT: Dendritic cells (DC) are the most important antigen presenting cells and play a pivotal role in host immunity to infectious agents by acting as a bridge between the innate and adaptive immune systems. Myeloid DCs (mDC) were isolated from peripheral blood and co-cultured with conidia (con) and germlings (ks) of Aspergillus fumigatus knockout (mitA, mnt1, rodA) and wildtype (wt) strains for 6 hours at an MOI of 1. RNA was extracted and hybridised to microarrays. Microarrays contain probes for approximately 110 selected human immune-relevant genes, including cytokine and chemokine genes, their receptors and downstream innate immunity genes. We used microarrays to detail the gene expression of human myeloid dendritic cells after 6h of co-cultivation with Aspergillus fumigatus wildtype and knockout mutants

ORGANISM(S): Homo sapiens

SUBMITTER: Susanne Kneitz

PROVIDER: E-GEOD-34884 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Differential gene expression in human myeloid dendritic cells interacting with different knockout strains of Aspergillus fumigatus in vitro

Project description:Dendritic cells (DC) are the most important antigen presenting cells and play a pivotal role in host immunity to infectious agents by acting as a bridge between the innate and adaptive immune systems. Myeloid DCs (mDC) were isolated from peripheral blood and co-cultured with conidia (con) and germlings (ks) of Aspergillus fumigatus knockout (mitA, mnt1, rodA) and wildtype (wt) strains for 6 hours at an MOI of 1. RNA was extracted and hybridised to microarrays. Microarrays contain probes for approximately 110 selected human immune-relevant genes, including cytokine and chemokine genes, their receptors and downstream innate immunity genes.

2012-04-17 | GSE34884 | GEO

The temporal dynamics of differential gene expression in human alveolar epithelial and endothelial cells interacting with the human pathogenic mould Aspergillus fumigatus in vitro

Project description:Aspergillus fumigatus is the most relevant pathogenic mould in immunocompromised patients. Spores of A. fumigatus are inhaled and reach the lung alveoli, where they interact with the human immune system. In this set of experiments, we co-cultured with defined morphologies of Aspergillus fumigatus (Af293) for 0h, 3h and 6h with either cells representing human alveolar epithelium (A549) or human alveolar endothelium (HPAEC). We included either monocyte-derived or myeloid dendritic cells from volunteer donor blood to the epithelial layer to examine their effect on gene expression. RNA was extracted from both cell lines at each time point and hybridised to microarrays. Microarrays contain probes for approximately 110 selected human immune-relevant genes, including cytokine and chemokine genes, their receptors and downstream innate immunity genes. We used microarrays to detail the gene expression of human alveloar epithelial and endothelials cells after 3h and 6h of co-cultivation with Aspergillus fumigatus and monocyte-derived or myeloid dendritic cells

2012-04-16 | E-GEOD-28806 | biostudies-arrayexpress

The temporal dynamics of differential gene expression in human alveolar epithelial and endothelial cells interacting with the human pathogenic mould Aspergillus fumigatus in vitro

2012-04-17 | GSE28806 | GEO

Gene expression profiles of human immature dendritic cells after 3h, 6h and 12h of co-cultivation with Aspergillus fumigatus

Project description:Gene expression profiles of human immature dendritic cells after 3h, 6h, 9h and 12h of co-cultivation with Aspergillus fumigatus were compared to expression profiles from human immature dendritic cells after 3h, 6h, 9h and 12h of cultivation. We used microarrays to detail the gene expression of human immature dendritic cells after 3h, 6h, 9h and 12h of co-cultivation with Aspergillus fumigatus

2011-03-29 | E-GEOD-21353 | biostudies-arrayexpress

The In Vitro Interaction of Aspergillus fumigatus and Human immature Dendritic Cells

Project description:Dendritic cells (DC) play an important role in host immunity by acting as a bridge between the innate and adaptive immune systems. They are antigen presenting cells that obtain microbial antigens by direct phagocytosis of the microbe or by cross presentation of antigens taken up from the surrounding environment. Monocyte derived DC were co-cultured with resting conidia of Aspergillus fumigatus at an MOI of 5 for 12 hours, cells were sampled every three hours. RNA was extracted from both organisms at each time point and hybridised to micro-arrays, whole genome Aspergillus fumigatus array (JCVI) and a custom immune array for DC. The genes up-regulated by DC in the presence of A. fumigatus indicated that the cells were producing a pro-inflammatory response. There was an increase in IL8 expression over time confirming its association with germ tube emergence. Over the course of the experiment there was increased expression of 210 genes by A. fumigatus, GO analysis indicated significant up-regulation of the following biological processes: fermentation, drug transport, pathogenesis, transport, tyrosine catabolism and response to oxidative stress. There were two clusters of temporally regulated genes showing up regulation before 6hr and after 6 hrs. This may be related to the increased mortality exhibited in DC at 6h. The initial analysis of A. fumigatus gene expression in response to DC shows similarity to its response to neutrophils with an up-regulation in catabolism and response to oxidative stress. A. fumigatus AF293 cells were grown in the presence and absence of human dendritic cells for 0h - 12h. Hybridizations were performed with biological replicates and flip-dye pairs.

2010-07-01 | E-GEOD-22053 | biostudies-arrayexpress

RNA-seq analysis of wildtype Aspergillus fumigatus A1160p+, ∆devR and ∆acdX in the presence and absence of Olorofim

Project description:Deletion of transcription factors DevR and AcdX in Aspergillus fumigatus causes increased/decreased susceptibility to the antifungal Olorofim. In order to characterise the basis of differential Olorofim susceptibility, and distinguish which metabolic pathways these transcription factors regulate, RNA-seq analysis was used to compare these transcription factor knockout mutants to wildtype A. fumigatus in both the presence and absense of Olorofim.

2022-10-14 | E-MTAB-10590 | biostudies-arrayexpress

Impaired calcineurin signaling in dendritic cells and macrophages increases susceptibility to aspergillosis through pentraxin-3 downregulation

Project description:Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-NFAT pathway, such as Cyclosporine A or Tacrolimus, are commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threating conditions. A component of the A. fumigatus cell wall, β-glucan, is recognized by dendritic cells via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important anti-fungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.

2016-12-31 | GSE71936 | GEO

Temporal dynamics of human cells co-cultivated with Aspergillus fumigatus

Project description:This SuperSeries is composed of the following subset Series: GSE21353: Gene expression profiles of human immature dendritic cells after 3h, 6h and 12h of co-cultivation with Aspergillus fumigatus GSE28806: The temporal dynamics of differential gene expression in human alveolar epithelial and endothelial cells interacting with the human pathogenic mould Aspergillus fumigatus in vitro Refer to individual Series

2012-04-16 | E-GEOD-28809 | biostudies-arrayexpress

Expression data from pDC infected with Aspergillus fumigatus

Project description:Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors responsible for hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2 but not Dectin-1 participates in hyphal recognition by pDCs and that Dectin-2 acts in cooperation with the FcRÎ³ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. Thus, these structures closely resembled those of neutrophil extracellular traps (NETs). Microarray analysis of the pDC transcriptome upon A. fumigatus infection demonstrated up-regulated expression of genes previously associated with viral infections or apoptosis. Moreover, the abundant expression of type I Interferon-encoding genes seen in CpG-stimulated pDCs was absent in the pDCs infected with A. fumigatus hyphae. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2. This interaction leads to formation of pET and triggers a distinct pattern of pDC gene expression. The spectrum of changes in gene expression was examined in pDCs from 3 blood donors, 2 and 4h following incubation with hyphae. Comparative controls included unstimulated and CpG-stimulated pDCs.

2014-03-01 | E-GEOD-55467 | biostudies-arrayexpress

Gene expression profiles of human immature dendritic cells after 3h, 6h and 12h of co-cultivation with Aspergillus fumigatus

2011-03-29 | GSE21353 | GEO

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