Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA189790 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat to human health throughout the world. Rodent MRSA pneumonia models mainly focus on the early innate immune responses to MRSA infection. However, the molecular pattern and mechanisms of recovery from MRSA lung infection are largely unknown. In this study, a nonlethal mouse MRSA pneumonia model was employed to investigate events during lung recovery from MRSA infection. We compared lung bacterial clearance, bronchoalveolar lavage fluid (BALF) characterization, lung histology, and gene expression profiling between Day 1 and Day 3 post-MRSA infection. Compared to Day 1 post-infection, bacterial colony counts and both BALF total cell number and protein concentration significantly decreased at Day 3 post-infection. Lung cDNA microarray analysis identified 47 significantly up-regulated and 35 down-regulated genes (p<0.01, 1.5-fold change [up and down]). Changes in eight genes were confirmed by real-time PCR. The pattern of gene expression suggests lung recovery is characterized by enhanced cell division, vascularization, and wound healing and by adjustment in host adaptive immune responses. Collectively, this data helps elucidate the molecular mechanisms of lung recovery after MRSA infection. RNA expression analysis was performed using the Illumina MouseRef-8 v2.0 BeadChip (Illumina, San Diego, CA), which provides coverage of approximately 25,700 genes and expressed sequence tags. Four independent mouse lung tissue samples at Day 1 and Day 3 post-MRSA infection were used in this study.
2013-11-12 | E-GEOD-36587 | biostudies-arrayexpress
Project description:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat to human health throughout the world. Rodent MRSA pneumonia models mainly focus on the early innate immune responses to MRSA infection. However, the molecular pattern and mechanisms of recovery from MRSA lung infection are largely unknown. In this study, a nonlethal mouse MRSA pneumonia model was employed to investigate events during lung recovery from MRSA infection. We compared lung bacterial clearance, bronchoalveolar lavage fluid (BALF) characterization, lung histology, and gene expression profiling between Day 1 and Day 3 post-MRSA infection. Compared to Day 1 post-infection, bacterial colony counts and both BALF total cell number and protein concentration significantly decreased at Day 3 post-infection. Lung cDNA microarray analysis identified 47 significantly up-regulated and 35 down-regulated genes (p<0.01, 1.5-fold change [up and down]). Changes in eight genes were confirmed by real-time PCR. The pattern of gene expression suggests lung recovery is characterized by enhanced cell division, vascularization, and wound healing and by adjustment in host adaptive immune responses. Collectively, this data helps elucidate the molecular mechanisms of lung recovery after MRSA infection.
2013-11-12 | GSE36587 | GEO
Project description:In order to explore the mechanism of host immune response after infection with MRSA (USA300 clone) pneumonia, we established a mouse animal infection model and took lung tissue for RNA sequencing. Then We performed gene expression profiling using RNA-seq data obtained from lung tissues at five time points.
2023-03-01 | GSE220943 | GEO
Project description:Influenza infection is substantially worsened by the onset of secondary pneumonia caused by bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). The bidirectional interaction between the influenza-injured lung microenvironment and MRSA is poorly understood. By conditioning MRSA ex vivo in bronchoalveolar lavage fluid collected from mice at various timepoints of influenza infection, we found that the influenza-injured lung microenvironment dynamically induces MRSA to increase cytotoxin expression while decreasing metabolic pathways. LukAB, a SaeRS two-component system dependent cytotoxin, is particularly important to the severity of post-influenza MRSA pneumonia. LukAB’s activity is likely shaped by the post-influenza lung microenvironment, as LukAB binds to (and is activated by) heparan sulfate (HS) oligosaccharide sequences shed from the epithelial glycocalyx after influenza. Our findings indicate that post-influenza MRSA pneumonia is shaped by bidirectional host-pathogen interactions: host injury triggers changes in bacterial expression of toxins, the activity of which may be shaped by host-derived HS fragments.
2022-11-29 | GSE199707 | GEO
Project description:During influenza pneumonia, the alveolar epithelial cells of the lungs are targeted by influenza virus. The distal airway stem cells (DASCs) and proliferating alveolar type II (AT2) cells are reported to be putative lung repair cells. However, their relative spatial and temporal distribution is still unknown during influenza-induced acute lung injury. Here, we investigated the distribution of these cells, and concurrently performed global proteomic analysis of the infected lungs to elucidate and link the cellular and molecular events during influenza pneumonia recovery. BALB/c mice were infected with a sub-lethal dose of influenza H1N1 virus. From 5 to 25 days post-infection (dpi), mouse lungs were subjected to histopathologic and immunofluorescence analysis to probe for global distribution of lung repair cells (using P63 and KRT5 markers for DASCs; PCNA and SPC markers for AT2 cells). At 7 and 15 dpi, infected mouse lungs were also subjected to protein mass spectrometry for relative protein quantification. DASCs appeared only in the damaged area of the lung from 7 dpi onwards, reaching a peak at 21 dpi, and persisted at 25 dpi. However, no differentiation of DASCs to AT2 cells was observed by 25 dpi. In contrast, AT2 cells began proliferating from 7 dpi to replenish its population. Mass spectrometry and gene ontology analysis revealed prominent innate immune response at 7 dpi, which shifted towards adaptive immune responses by 15 dpi. Hence, proliferating AT2 cells but not DASCs contribute to AT2 cell regeneration following transition from innate to adaptive immune responses during the early phase of recovery from influenza pneumonia up to 25 dpi.
2020-04-17 | PXD014967 | Pride
Project description:A leading cause of morbidity and mortality during influenza infection is the development of a secondary bacterial pneumonia, which is appropriately treated with antibiotics. In the absence of a bacterial superinfection, prescribing antibiotics is not indicated but has nevertheless become a common clinical practice for those presenting with a respiratory viral illness. We found that antibiotic use during an antecedent influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistantStaphylococcus aureus(MRSA). The antibiotics perturbed the gut microbiome causing a fungal dysbiosis that drives an increase in lung eosinophils. We also demonstrate eosinophils, through the release of major basic protein, impair macrophage ability to clear MRSA. Moreover, we provide clinical evidence that eosinophils positively correlate with antibiotic use and worsened outcomes in patients hospitalized for viral infections. Altogether, our work establishes a counterproductive effect of antibiotic treatment during influenza infection that have negative immunologic consequences in the lungs thereby increasing the risk of developing a secondary bacterial infection.
2024-08-21 | GSE243542 | GEO
Project description:A leading cause of morbidity and mortality during influenza infection is the development of a secondary bacterial pneumonia, which is appropriately treated with antibiotics. In the absence of a bacterial superinfection, prescribing antibiotics is not indicated but has nevertheless become a common clinical practice for those presenting with a respiratory viral illness. We found that antibiotic use during an antecedent influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistantStaphylococcus aureus(MRSA). The antibiotics perturbed the gut microbiome causing a fungal dysbiosis that drives an increase in lung eosinophils. We also demonstrate eosinophils, through the release of major basic protein, impair macrophage ability to clear MRSA. Moreover, we provide clinical evidence that eosinophils positively correlate with antibiotic use and worsened outcomes in patients hospitalized for viral infections. Altogether, our work establishes a counterproductive effect of antibiotic treatment during influenza infection that have negative immunologic consequences in the lungs thereby increasing the risk of developing a secondary bacterial infection.
2024-08-21 | GSE259429 | GEO
Project description:The Staphylococcus aureus Panton Valentine leukocidin (PVL) is a pore-forming toxin secreted by strains epidemiologically associated with the current outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and with the often lethal necrotizing pneumonia. To investigate the role of PVL in pulmonary disease, we tested the pathogenicity of clinical isolates, isogenic PVL-negative and PVL-positive S. aureus strains, as well as purified PVL, in a mouse acute pneumonia model. Here we show that PVL is sufficient to cause pneumonia and that the expression of this leukotoxin induces global changes in transcriptional levels of genes encoding secreted and cell-wall-anchored staphylococcal proteins, including the lung inflammatory factor staphylococcal protein A (Spa). Keywords: comparative transcription profile in the presence or absence of PVL toxin
2007-02-13 | GSE6985 | GEO
Project description:Influenza-induced respiratory failure is substantially worsened by secondary bacterial infections such as methicillin-resistant Staphylococcus aureus (MRSA). The bidirectional interaction between the influenza-injured lung microenvironment and MRSA is poorly understood. By conditioning MRSA ex vivo in bronchoalveolar lavage (BAL) fluid collected from mice at various timepoints of influenza infection, we found that influenza-injured lung microenvironment induces MRSA to increase cytotoxin expression while decreasing metabolic pathways. This overall increase in MRSA virulence was dependent upon SaeRS, a bacterial two-component system. Once expressed by MRSA, these influenza-induced toxins (such as Hla and LukAB) interact with host heparan sulfate (HS) fragments shed into the airspace. Highly-sulfated HS fragments augmented Hla- and LukAB-toxicity in vitro and in vivo. Our findings indicate that post-influenza MRSA pneumonia is shaped by bidirectional host-pathogen interactions: host injury triggers changes in bacterial expression of toxins, the activity of which are then shaped by host-derived HS fragments.
2022-11-29 | GSE199708 | GEO
Project description:Regulatory T (Treg) cells promote recovery from lung injury. Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia.
2021-02-18 | GSE151541 | GEO