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Transcriptome study of A. fumigatus hyphae and human neutrophils

ABSTRACT: The infections with the human pathogenic fungus A. fumigatus is an emerging problem. The infections process and the reaction of the immune systeme to the infection is still not complete understood. So we analyzed the response of A. fumigatus to human neutrophils to get insights of these interaction.

ORGANISM(S): Aspergillus fumigatus CEA10

PROVIDER: GSE55648 | GEO | 2018/01/31

REPOSITORIES: GEO

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Transcription profiling of Aspergillus fumigatus hyphae and conidia after incubation with neutrophils from different donors

Project description:Hyphae and conidia, representing the two developmental stages of the fungus, were examined separately in this study. RNA from hyphae or conidia incubated in plasma in RPMI/HEPES without neutrophils was used as reference, and was co-hybridized with the query samples obtained from the corresponding sets incubated with neutrophils. Each biological replicate was carried out with neutrophils obtained from a different donor, and the RNA samples associated with each neutrophil source was paired separately with a corresponding reference sample prepared at the same time.

2008-09-25 | E-MEXP-1722 | biostudies-arrayexpress

Transcriptomic study of the pathogenic fungus Aspergillus fumigatus during a murine intranasal infection, using the Whole A. fumigatus Genome Expression 44K v.1 microarray (AWAFUGE).

Project description:Aspergillus fumigatus is a saprophytic mold capable of reaching the human deep respiratory system causing different diseases. In this study we tried to detect the virulence mechanisms developed by the fungus, using four days evolution murine intranasal infection model. For that, we develop three independent infections, in order to obtain three independent fungus samples from the lung of the infected mice per day study. Finally, we had 12 independent samples from 12 different infected mice.

2018-12-03 | E-MTAB-5314 | biostudies-arrayexpress

Effect of Artemisinin on Aspergillus fumigatus gene expression program

Project description:We examined the antifungal activity of artemisinin against Aspergillus fumigatus (A. fumigatus), a pathogenic filamentous fungus responsible for allergic and invasive aspergillosis in humans and analyzed transcript profiles of the fungus on exposure to Artemisinin. A. fumigatus spores were cultured for 48 h and then treated with artemisinin (at MIC50 concentration) or solvent control (DMSO) for 3 h to study its transcriptomic profiles.

2011-05-11 | GSE21297 | GEO

Aspergillus fumigatus melanin manipulates the cargo and kinetics of neutrophil-derived extracellular vesicles

Project description:Neutrophil-derived extracellular vesicles have regained scientific interest as potent ‘wireless’ modulators with pleiotropic effects on the immune system. A few studies have addressed their role in the context of microbial pathogenesis showing their bacteriostatic effects against Staphylococcus aureus in vitro and their potential as diagnostic markers in the onset of bacterimic sepsis in vivo. Here, we provided first insights into the vesicle release driven by the clinically relevant pathogenic fungus Aspergillus fumigatus that causes invasive infections in immunocompromised individuals worldwide often with a lethal outcome. Neutrophils, stimulated with fungal spores, potently produced vesicles that we refer as anti-fungal extracellular vesicles (afEVs). We revealed that the conidial surface pigment of A. fumigatus dihydroxynaphthalene (DHN) melanin - a well known fungal virulence factor - is a key ‘switch-on/off’ governing vesicle production. We profiled the kinetics of afEV formation and showed that DHN-melanin interferes with the vesicle number, vesicle surface maturation markers such as CD11b, CD63 and CD177 and governs the enrichment of distinct afEV subpopulations unrelated to apoptosis. Simultaneously we tracked down the fate of neutrophils during afEV formation and observed mulivesicular body formation that led to active export of CD11b, CD63 and CD177 by shedding from the surface of neutrophils onto the surface afEVs. By dissecting the proteome cargo of afEVs produced against wild-type and melanin-free conidia we verified that DHN-melanin also manipulates the type of cargo neutrophils accumulate in the vesicles upon confronting conidia with different cell wall integrity. afEVs contained higher amounts of antimicrobial peptides than spontaneously released EVs from uninfected neutrophils. Last but not least afEVs exhibit fungistatic effects and also modulate cell wall morphogenesis of hyphae.

2019-05-17 | PXD005994 | Pride

Healthy peripheral neutrophils total RNA-Seq: Serum Amyloid P component is an essential element of resistance against Aspergillus fumigatus

Project description:Serum amyloid P component (SAP; APCS gene, also known as Pentraxin 2, PTX2), is a component of the humoral arm of innate immunity involved in resistance to bacterial infection and regulation of tissue remodeling. The present study was designed to investigate the role of SAP/PTX2 in antifungal resistance. SAP-deficient Apcs-/- mice showed a dramatic increase in susceptibility to A. fumigatus infection. The defective anti-fungal resistance of gene targeted mice was rescued by in vitro opsonization of A. fumigatus conidia and in vivo administration of murine SAP. Mouse and human SAP bound conidia, activated the complement cascade and increased phagocytosis by mouse and human neutrophils. Defective resistance of Apcs-/- SAP-deficient mice was associated with defective in vivo recruitment of neutrophils and phagocytosis in the lungs. The opsonic activity of SAP was dependent on the classical pathway of complement activation. In immunosuppressed mice, SAP administration protected hosts against A. fumigatus infection and death. In the context of a study of hematopoietic stem-cell transplantation, genetic variation in the human APCS gene was associated with susceptibility to invasive pulmonary aspergillosis. Thus, SAP is a fluid phase pattern recognition molecule essential for resistance against A. fumigatus. The results reported here also suggest that SAP has therapeutic potential against an infectious agent which represents a formidable clinical challenge.

2021-04-20 | GSE163533 | GEO

Differentiated PLB-985 cells as a model system for Aspergillus fumigatus infection

Project description:Fungal infections remain a tremendous source of global morbidity and mortality, with more than 1 billion individuals affected by fungal infections each year. Invasive infections are particularly dangerous and kill numbers on par with tuberculosis or malaria. Aspergillus fumigatus is a major source of invasive fungal infections in humans, and is particularly dangerous to the immunocompromised. In many cases, research into invasive fungal infections is limited by a lack of model systems. In this study we hypothesized that cultured, differentiated human PLB-985 neutrophil-like cells could serve as model system to study the host-pathogenesis of A. fumigatus. We tested this hypothesis by defining the phagocytosis and intracellular trafficking of A. fumigatus conidia by PLB-985 cells, the production of neutrophil extracellular traps, and by characterizing extracellular vesicles produced in response to infection. As part of this analysis, we performed a detailed LC-MS/MS-based proteomic comparison of extracellular vesicles isolated by two different methods, centrifugation-based isolation or size-exclusion chromatography. We find numerous similarities between primary neutrophils and PLB-985 cells that suggest differentiated PLB-985 cells can serve as a tractable in vitro model system for further study of many aspects of A. fumigatus pathogenesis.

2021-07-30 | PXD027032 | Pride

Comparison of Aspergillus fumigatus transcriptome grown on selected nitrogen sources

Project description:Transcriptome of A. fumigatus shifted from ammoniumtartrate to different nitrogen sources and incubated for a defined time was compared. After 16h preculture, the fungus was transferred into fresh medium containing ammonium tartrate, sodium nitrate, proline or bsa as nitrogen source. After 1h, fungus was reisolated, RNA was prepared from fungus, transcriptome was assessed and used for further analysis.

2011-10-30 | GSE30384 | GEO

Effect of amphotericin B on Aspergillus fumigatus

Project description:Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections including invasive aspergillosis. We aimed to understand molecular targets of AMB in Aspergillus fumigatus (Afu) by genomic approaches. Keywords: Aspergillus fumigatus treated with amphotericin B for 24 hours

2008-02-14 | GSE10505 | GEO

Transcriptome response of Aspergillus fumigatus cultures under different temperatures

Project description:Microarray analysis was used to compare gene expression of Aspergillus fumigatus under two different sporulation temperatures, 17oC and 32oC, with an emphasis on genes encoding known or putative allergens of the fungus. The objective of the study was to investigate whether allergenic potencies of A. fumigatus spores produced under different sporulation temperatures would be influenced by temperature-dependent transcriptional regulation of allergenicity genes.

2009-06-16 | GSE16617 | GEO

The responses of the pulmonary pathogen Aspergillus fumigatus to the neutrophil derived oxidant N- chlorotaurine

Project description:Aspergillus fumigatus is a pulmonary pathogen to individuals who are immunocompromised (e.g. mylosuppression) and those who display defects in immune equilibrium, commonly observed in the Cystic fibrosis lung and presents itself in the form as allergic bronchopulmonary aspergillosis.32 In the latter disease A. fumigatus airborne conidia penetrate the lower airways, germinate and and grow within in thick tenacious CF mucus. A. fumigatus CF colonized individuals can become sensitized to A. fumigatus secreted allergens and eventually develop a type 2 hypersensitivity reaction to AF allergens, toxins and proteases which are readily replenished into the mucus which can directly cause cell damage and peeling at the bronco – epithelium interface. A. fumigatus also induces invasive disease which carries up to 90% mortality. The effect of neutrophil oxidant NCT on A. fumigatus was determined as neutrophils are the first line of cellular defense against A. fumigatus.

2018-12-19 | PXD009853 | Pride

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