Neutrophil gene expression in response to Mycobacterium abscessus
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Ken Malcolm
PROVIDER: E-GEOD-39889 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The response of human neutrophils to the emerging pathogen Mycobacterium abscessus has not been described. However, M. abscessus infections are frequently associated with neutrophil-rich abscesses. To better understand the reponse of neutrophils to M. abscessus we performed gene expression analysis using Affymetrix HG-U133A Plus 2.0 microarrays. Human neutrophils from healthy donors were stimulated with isogenic rough and smooth morphotypes of M. abscessus. Staphylococcus aureus was used as a control. Gene expression was compared to neutrophils left unstimulated. Neutrophils from four individual donors were isolated on separate days and stimulated with freshly prepared bacteria. Neutrophils (stimulated and control) were left for 2 hours before total RNA was isolated, and biotinylated cRNA was prepared by standard methods. Analysis indicates that M. abscessus morphotypes induce a limited number of genes, when compared to S. aureus, which are enriched in genes for cytokines and chemokines, including neutrophil-specific chemokines. These data suggest that neutrophils have a limited response to M. abscessus, which may contribute to neutrophil-rich abscess formation.!Series_overall_design = Human neutrophils from healthy donors were exposed to rough Mab (ATCC 19977T), smooth Mab (ATCC 19977T) and S. aureus (CF clinical strain) for two hours; control cells were exposed to saline.
2013-01-10 | GSE39889 | GEO
Project description:Mycobacterium abscessus is an emerging pathogen causing pulmonary infections in those with inflammatory lung disorders, such as Cystic Fibrosis (CF), and is associated with the highest fatality rate among rapidly growing mycobacteria (RGM). Phenotypically, MAB manifests as either a Smooth (MAB-S) or a Rough (MAB-R) morphotype, which differ in their levels of cell wall glycopeptidolipids (GPLs) and in their pathogenicity in vivo. As one of the primary immune cells encountered by MAB, we sought to examine the early transcriptional events within macrophages, following infection with both MAB-S or MAB-R. We sampled the small RNA (sRNA) transcriptome of THP-1-derived macrophages infected with both MAB-R and MAB-S at 1, 4 and 24 hours post-infection (hpi) using RNA-seq. MAB-S elicited a more robust transcriptional response at the miRNA level, reflecting higher cytokine levels in culture supernatants. However, and a direct comparison identified no differentially expressed miRNAs between MAB-R- and MAB-S-infected cells. Most of the induced miRNAs have previously been associated with mycobacterial infection and overall miRNA expression patterns were similarly highly correlated between the morphotypes. THP-1-derived macrophages were infected in parallel with the MAB-R and MAB-S morphotypes. Poly-A selected RNAs were purified and sequenced at 1, 4 and 24 hours post-infection, and compared with uninfected controls.
2015-09-09 | E-GEOD-72821 | biostudies-arrayexpress
Project description:Mycobacterium abscessus is an emerging pathogen causing pulmonary infections in those with inflammatory lung disorders, such as Cystic Fibrosis (CF), and is associated with the highest fatality rate among rapidly growing mycobacteria (RGM). Phenotypically, MAB manifests as either a Smooth (MAB-S) or a Rough (MAB-R) morphotype, which differ in their levels of cell wall glycopeptidolipids (GPLs) and in their pathogenicity in vivo. As one of the primary immune cells encountered by MAB, we sought to examine the early transcriptional events within macrophages, following infection with both MAB-S or MAB-R. We sampled the small RNA (sRNA) transcriptome of THP-1-derived macrophages infected with both MAB-R and MAB-S at 1, 4 and 24 hours post-infection (hpi) using RNA-seq. MAB-S elicited a more robust transcriptional response at the miRNA level, reflecting higher cytokine levels in culture supernatants. However, and a direct comparison identified no differentially expressed miRNAs between MAB-R- and MAB-S-infected cells. Most of the induced miRNAs have previously been associated with mycobacterial infection and overall miRNA expression patterns were similarly highly correlated between the morphotypes. THP-1-derived macrophages were infected in parallel with the MAB-R and MAB-S morphotypes. Size-selected small RNAs were purified and sequenced at 1, 4 and 24 hours post-infection, and compared with uninfected controls.
2015-09-09 | E-GEOD-72769 | biostudies-arrayexpress
Project description:Mycobacterium abscessus (Mab) infection can be a deadly infection in patients with chronic lung disease like cystic fibrosis. In vitro and in vivo, Mab may adopt a smooth (S) or rough (R) morphotype, the latter with fewer cell wall glycopeptidolipids. Although there are studies of the host response against constitutive Mab-S and Mab-R, we report the first analysis of early transcriptional events and responses in mouse bone marrow derived macrophages (BMDMs) upon infection with our media-selected, isogenic, interchangeable Mab-S and Mab-R. The early transcriptional events after infection with both the morphotypes showed considerable overlap of the pro-inflammatory genes that were differentially regulated compared to the uninfected macrophages. However, we also observed some signature genes which were upregulated during Mab-S compared to Mab-R infections. Media selected Mab-S and Mab-R behave in a similar fashion to constitutive S and R types with respect to pathogenesis and immune response and will likely be a better model of in vivo infection than multiply passaged, mutated organisms.
2023-01-31 | GSE221966 | GEO
Project description:Mycobacterium abscessus is an emerging pathogen causing pulmonary infections in those with inflammatory lung disorders, such as Cystic Fibrosis (CF), and is associated with the highest fatality rate among rapidly growing mycobacteria (RGM). Phenotypically, MAB manifests as either a Smooth (MAB-S) or a Rough (MAB-R) morphotype, which differ in their levels of cell wall glycopeptidolipids (GPLs) and in their pathogenicity in vivo. As one of the primary immune cells encountered by MAB, we sought to examine the early transcriptional events within macrophages, following infection with both MAB-S or MAB-R. We sampled the small RNA (sRNA) transcriptome of THP-1-derived macrophages infected with both MAB-R and MAB-S at 1, 4 and 24 hours post-infection (hpi) using RNA-seq. MAB-S elicited a more robust transcriptional response at the miRNA level, reflecting higher cytokine levels in culture supernatants. However, and a direct comparison identified no differentially expressed miRNAs between MAB-R- and MAB-S-infected cells. Most of the induced miRNAs have previously been associated with mycobacterial infection and overall miRNA expression patterns were similarly highly correlated between the morphotypes.
2015-09-09 | GSE72821 | GEO
Project description:Mycobacterium abscessus is an emerging pathogen causing pulmonary infections in those with inflammatory lung disorders, such as Cystic Fibrosis (CF), and is associated with the highest fatality rate among rapidly growing mycobacteria (RGM). Phenotypically, MAB manifests as either a Smooth (MAB-S) or a Rough (MAB-R) morphotype, which differ in their levels of cell wall glycopeptidolipids (GPLs) and in their pathogenicity in vivo. As one of the primary immune cells encountered by MAB, we sought to examine the early transcriptional events within macrophages, following infection with both MAB-S or MAB-R. We sampled the small RNA (sRNA) transcriptome of THP-1-derived macrophages infected with both MAB-R and MAB-S at 1, 4 and 24 hours post-infection (hpi) using RNA-seq. MAB-S elicited a more robust transcriptional response at the miRNA level, reflecting higher cytokine levels in culture supernatants. However, and a direct comparison identified no differentially expressed miRNAs between MAB-R- and MAB-S-infected cells. Most of the induced miRNAs have previously been associated with mycobacterial infection and overall miRNA expression patterns were similarly highly correlated between the morphotypes.
2015-09-09 | GSE72769 | GEO
Project description:Bronchial Epithelial cells were exposed to microparticles generated from mycobacterium abscessus MAB cell wall per an in-house protocol. Control group was exposed to saline. Differentially expressed genes related to MAB cell wall particles were determined.
2020-08-16 | GSE140437 | GEO
Project description:In this study, we were interested to get deeper insights into the molecular mechanisms that govern the formation and selection of the different colony morphologies in Mycobacterium abscessus strains, including the potential reversibility of the rough (R) phenotype into a smooth (S) phenotype. We used next generation sequencing (NGS) and micro-array / RNAseq approaches to determine the genome sequences and transcriptomic profiles of three isogenic S/R strain couples of M. abscessus. One clinical isolate strain named CF and two collection strains referred as 19977-AT and 19977-IP. To perform the transcriptomic comparison of the rough variant versus the smooth variant for each M. abscessus strain, a customized micro-array has been manufactured by Agilent (8 x 15k format). The design of oligonucleotides covering all protein coding sequences was done using OligoArray version 2.1 on the basis of the 4920 predicted coding sequences composing the entire M. abscessus genome. The experimental data for each of the 3 strains consisted of 6 hybridizations (3 biological replicates with dye-swap).
2013-05-15 | E-GEOD-37984 | biostudies-arrayexpress
Project description:Identification of molecular key determinants of the Mycobacterium abscessus smooth and rough morphotypes through transcriptome analyses
| PRJNA166871 | ENA
Project description:The initial interactions between a host cell and a pathogen can dictate disease outcomes and are important targets for host-directed therapies. Mycobacterium abscessus (Mab) is a highly antibiotic resistant, rapidly growing non-tuberculous mycobacterium that infects patients with chronic lung diseases, like cystic fibrosis. Mab can infect host immune cells, such as macrophages, which contribute to its pathogenesis. However, our understanding of host genes that modulate the initial host-Mab interactions remains unclear. Here, we developed a functional genetic approach by coupling a Mab fluorescent reporter with a genome-wide knockout library in murine macrophages. We used this approach to conduct a forward genetic screen to uncover host genes that contribute to the uptake of Mab by macrophages. We identified known regulators of phagocytosis, such as the integrin Itgb2, and uncovered a key requirement for glycosaminoglycan (sGAG) synthesis for macrophages to efficiently bind to Mab. CRISPR-Cas9 targeting of three key sGAG biosynthesis regulators, UGDH, B4GALT7 and B3GAT3 resulted in reduced uptake of both smooth and rough Mab variants by macrophages. Mechanistic studies suggest that sGAGs function upstream of pathogen engulfment and are required for uptake of Mab but not Escherichia coli or latex beads. Further investigation found that the loss of sGAGs reduces the surface expression, but not the mRNA expression, of key integrins, suggesting a key role for sGAGs in modulating surface receptor availability. Together these studies globally defined and characterized important regulators of macrophage-Mab interactions and are a first step better understand important host genes that contribute to Mab pathogenesis and disease.
2023-01-13 | GSE221413 | GEO