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Functional genomics of human bronchial epithelial cells directly interacting with conidiospores of Aspergillus fumigatus

ABSTRACT: The cells of the airway epithelium play critical roles in host defense to inhaled irritants, and in asthma pathogenesis. These cells are constantly exposed to conidiospores of the ubiquitous mould Aspergillus fumigatus, which are small enough to reach the alveoli. This exposure is asymptomatic in most individuals but can be associated with a spectrum of diseases ranging from asthma and allergic bronchopulmonary aspergillosis to aspergilloma and invasive aspergillosis. Airway epithelial cells have been shown to internalize A. fumigatus conidiospores in vitro, but the implications of this process for pathogenesis remain unclear. We have developed a cell culture model for this interaction using the 16HBE cell line and a transgenic A. fumigatus strain expressing green fluorescent protein. Using fluorescence-activated cell sorting (FACS), cells directly interacting with conidiospores and cells not associated with any conidiospores were sorted into separate samples. Transcriptional profiling of these samples using Agilent Whole Human Genome microarrays revealed significant changes in gene expression in response to interaction with conidiospores. The identification of biologically relevant responses validates this methodology, and motivates further work to characterize the interactions between A. fumigatus conidiospores and primary airway epithelial cells of normal and asthmatic origins.

ORGANISM(S): Homo sapiens

PROVIDER: GSE16627 | GEO | 2010/06/04

SECONDARY ACCESSION(S): PRJNA122791

REPOSITORIES: GEO

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Functional genomics of Aspergillus fumigatus conidiospores interacting with human bronchial epithelial cells

Project description:The cells of the airway epithelium play critical roles in host defense to inhaled irritants, and in asthma pathogenesis. These cells are constantly exposed to conidiospores of the ubiquitous mould Aspergillus fumigatus, which are small enough to reach the alveoli. This exposure is asymptomatic in most individuals but can be associated with a spectrum of diseases ranging from asthma and allergic bronchopulmonary aspergillosis to aspergilloma and invasive aspergillosis. Airway epithelial cells have been shown to internalize A. fumigatus conidiospores in vitro, but the implications of this process for pathogenesis remain unclear. We have developed a cell culture model for this interaction using the 16HBE cell line and a transgenic A. fumigatus strain expressing green fluorescent protein. The transcriptional profiles of A. fumigatus conidiospores incubated in the presence or absence of human cells were compared, revealing significant changes in fungal gene expression in response to conidial interaction with cells. Gene expression levels were investigated in A. fumigatus conidiospores incubated in the presence or absence of 16HBE cells for 6 hours. Four independent samples were analysed for each of these conditions, using JCVI PFGRC Aspergillus fumigatus Version 3 microarrays, with a dye-swap experimental design.

2011-06-01 | E-GEOD-16630 | biostudies-arrayexpress

Functional genomics of Aspergillus fumigatus conidiospores interacting with human bronchial epithelial cells

2011-06-01 | GSE16630 | GEO

Functional genomics of human bronchial epithelial cells interacting with conidiospores of Aspergillus fumigatus

2011-06-01 | GSE16628 | GEO

Functional genomics of human bronchial epithelial cells interacting with conidiospores of Aspergillus fumigatus

Project description:The cells of the airway epithelium play critical roles in host defense to inhaled irritants, and in asthma pathogenesis. These cells are constantly exposed to conidiospores of the ubiquitous mould Aspergillus fumigatus, which are small enough to reach the alveoli. This exposure is asymptomatic in most individuals but can be associated with a spectrum of diseases ranging from asthma and allergic bronchopulmonary aspergillosis to aspergilloma and invasive aspergillosis. Airway epithelial cells have been shown to internalize A. fumigatus conidiospores in vitro, but the implications of this process for pathogenesis remain unclear. We have developed a cell culture model for this interaction using the 16HBE cell line and a transgenic A. fumigatus strain expressing green fluorescent protein. Comparing the transcriptional profiles of control cells and cells exposed to A. fumigatus conidiospores using Agilent Whole Human Genome microarrays revealed significant changes in gene expression in response to the presence of conidiospores. The identification of biologically relevant responses validates this methodology, and motivates further work to characterize the interactions between A. fumigatus conidiospores and primary airway epithelial cells of normal and asthmatic origins. Gene expression levels were investigated in 16HBE cells incubated in the presence or absence of A. fumigatus conidiospores for 6 hours. Four independent cell samples were analysed for each of these conditions, using Agilent Whole Human Genome microarrays, with a one-colour experiemntal design.

2011-06-01 | E-GEOD-16628 | biostudies-arrayexpress

Functional genomics of human bronchial epithelial cells directly interacting with conidiospores of Aspergillus fumigatus

Project description:The cells of the airway epithelium play critical roles in host defense to inhaled irritants, and in asthma pathogenesis. These cells are constantly exposed to conidiospores of the ubiquitous mould Aspergillus fumigatus, which are small enough to reach the alveoli. This exposure is asymptomatic in most individuals but can be associated with a spectrum of diseases ranging from asthma and allergic bronchopulmonary aspergillosis to aspergilloma and invasive aspergillosis. Airway epithelial cells have been shown to internalize A. fumigatus conidiospores in vitro, but the implications of this process for pathogenesis remain unclear. We have developed a cell culture model for this interaction using the 16HBE cell line and a transgenic A. fumigatus strain expressing green fluorescent protein. Using fluorescence-activated cell sorting (FACS), cells directly interacting with conidiospores and cells not associated with any conidiospores were sorted into separate samples. Transcriptional profiling of these samples using Agilent Whole Human Genome microarrays revealed significant changes in gene expression in response to interaction with conidiospores. The identification of biologically relevant responses validates this methodology, and motivates further work to characterize the interactions between A. fumigatus conidiospores and primary airway epithelial cells of normal and asthmatic origins. Four independent samples of 16HBE cells incubated with GFP-expressing Aspergillus fumigatus conidiospores for 6 hours were analyzed by flow cytometry and divided into negative and positive samples based on the presence of a GFP signal, representing cells with no direct contact with conidiospores and cells directly interacting with conidiospores, respectively. Gene expression was analyzed in these 8 samples using Agilent Whole Human Genome microarrays, with a one-colour experiemntal design.

2010-06-16 | E-GEOD-16627 | biostudies-arrayexpress

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Project description:In lung diseases caused by the major mould pathogen Aspergillus fumigatus the pulmonary epithelium is destroyed by invasive growth of fungal hyphae, a process thought to require fungal proteases. Here we show that the A. fumigatus pH-responsive transcription factor PacC governs expression of secreted proteases during invasive lung infections and is required for epithelial invasion and pathogenicity. In addition, A. fumigatus M-NM-^TpacC mutants aberrantly remodel the fungal cell wall during infection. This study defines distinct PacC-mediated mechanisms of host damage during pulmonary aspergillosis. ch1: treatment protocol Temporal transcriptional profiling of ATCC46645 strain and isogenic M-NM-^TpacC Aspergillus fumigatus mutant during murine infection

2014-10-20 | E-GEOD-54810 | biostudies-arrayexpress

RNA-Seq of human dendritic cells from aspergillosis and asthma patients after challenge with Aspergillus fumigatus, SYBARIS project.

Project description:Aspergillosis covers a range of infections cause by Aspergillus species, and in many cases can be life threatening. Individuals with weakened immune systems are particularly at risk. Dendritic cells were derived from patients with allergic brochopulmonary aspergillosis (ABPA), chronic cavitary pulmonary aspergillosis (CCPA), and asthma, as well as from healthy donors. Each sample was split in two, and one sample from each pair was cultured with Aspergillus fumigatus. RNA-sequencing was used to assess transcriptional changes in the human cells in response to pathogen challenge. Many genes known to be important in immunity were found to exhibit differential expression after fungal challenge between healthy and diseased individuals, including chemokines and C-type lectins.

2016-04-30 | E-SYBR-3 | biostudies-arrayexpress

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

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. 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 microarray and proteomic methods. Keywords: Aspergillus fumigatus treated with amphotericin B for 24 hours Experiment was performed in dye swap manner from two different biological replicates

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