Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1219108 | ENA |
REPOSITORIES: ENA
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Project description:Characterization of host-pathogen interactions is critical for the development of next-generation therapies and vaccines. Classical approaches involve the use of transformed cell lines and/or animal models which may not reflect the complexity and response of the human host. We reconstituted the ciliated human bronchial epithelium in vitro using primary bronchial epithelial cells to simultaneously monitor the infection-linked global changes in nontypeable Haemophilus influenzae (NTHi) and infected host epithelia gene expression by dual RNA-seq. Acquisition of a total of nearly 2,5 billion sequences allowed construction of high-resolution strand-specific transcriptome maps of NTHi during infection of host mucosal surface and monitoring of metabolic as well as stress-induced host-adaptation strategies of this pathogen. As a part of our screening, we identified a global profile of noncoding transcripts that are candidate small RNAs regulated during human host infection in Haemophilus species. Temporal analysis of host mRNA signatures revealed significant dysregulation of target cell cytoskeleton elicited by bacterial infection, with a profound effect on intermediate filament network of bronchial epithelium. Our data provide a robust and comprehensive catalogue of regulatory responses that drive NTHi pathogenesis and gives novel insights into complex crosstalk between the host and the invading pathogen. Primary human bronchial epithelium was infected with NTHi at a multiplicity of 100:1. Total RNA was isolated at 1, 6, 24 and 72 h post-infection in three biologically-independent experiments and cDNA libraries were prepared and sequenced with Illumina HiSeq 2500 sequencer. At each time point, between 60 and 180 million total reads per sample were obtained of which approximately one-third could be aligned to non-rRNA regions of the bacterial and human genomes
2015-11-02 | E-GEOD-63900 | biostudies-arrayexpress
Project description:Characterization of host-pathogen interactions is critical for the development of next-generation therapies and vaccines. Classical approaches involve the use of transformed cell lines and/or animal models which may not reflect the complexity and response of the human host. We reconstituted the ciliated human bronchial epithelium in vitro using primary bronchial epithelial cells to simultaneously monitor the infection-linked global changes in nontypeable Haemophilus influenzae (NTHi) and infected host epithelia gene expression by dual RNA-seq. Acquisition of a total of nearly 2,5 billion sequences allowed construction of high-resolution strand-specific transcriptome maps of NTHi during infection of host mucosal surface and monitoring of metabolic as well as stress-induced host-adaptation strategies of this pathogen. As a part of our screening, we identified a global profile of noncoding transcripts that are candidate small RNAs regulated during human host infection in Haemophilus species. Temporal analysis of host mRNA signatures revealed significant dysregulation of target cell cytoskeleton elicited by bacterial infection, with a profound effect on intermediate filament network of bronchial epithelium. Our data provide a robust and comprehensive catalogue of regulatory responses that drive NTHi pathogenesis and gives novel insights into complex crosstalk between the host and the invading pathogen.
2015-11-02 | GSE63900 | GEO
Project description:Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigate how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed insignificant barrier damage and limited RSV infection. Single nuclear RNA-sequencing revealed age-related insufficiency of an anti-apoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium. Lastly, apoptotic inhibitor treatment of a neonatal mouse model of RSV infection ameliorated infection and inflammation in the lung. Taken together, our findings identify a STAT3-mediated anti-apoptosis pathway as a target to battle severe RSV disease in infants.
2024-09-30 | GSE274466 | GEO
Project description:This study is the first to show transfer of regulatory bacterial sRNAs from bacterial OMVs to host cells. Demonstration of transfer of bacterial sRNA from Pseudomonas aeruginosa OMVs to host cells in two cell types. RNA isolated from PA14 OMV exposed primary human bronchial epithelial cells or CFBE41o- bronchial epithelial cells as well as unexposed control cells was analyzed by small RNA-Seq. Primary cell exposures were performed on two donors and exposures of CFBE41o- cells were done in triplicate.
2016-05-13 | E-GEOD-80421 | biostudies-arrayexpress
Project description:Asthma is a very frequent airway disease that affects 6 to 20% of the population. Severe asthma, represents 3 to 5% of all asthmatic patients and is histologically characterized by an increased bronchial smooth muscle (BSM) mass and clinically by viral exacerbations. Functionally, BSM remodeling had a poor prognostic value in asthma, since higher BSM mass was associated with lower lung function and increased exacerbation rate. However, the role of BSM as a potential actor of asthma exacerbation has only been sparsely suggested. We thus hypothesis that asthmatic BSM cells could act on bronchial epithelium and modified its response to rhinovirus infection.
2023-05-02 | PXD015604 | Pride
Project description:Secondary bacterial infections (SBIs) exacerbate influenza-associated disease and mortality. Antimicrobial agents can reduce the severity of SBIs, but many have limited efficacy or cause adverse effects. Thus, new treatment strategies are needed. Kinetic models describing the infection process can help determine optimal therapeutic targets, the time scale on which a drug will be most effective, and how infection dynamics will change under therapy. To understand how different therapies perturb the dynamics of influenza infection and bacterial coinfection and to quantify the benefit of increasing a drug’s efficacy or targeting a different infection process, I analyzed data from mice treated with an antiviral, an antibiotic, or an immune modulatory agent with kinetic models. The results suggest that antivirals targeting the viral life cycle are most efficacious in the first 2 days of infection, potentially because of an improved immune response, and that increasing the clearance of infected cells is important for treatment later in the infection. For a coinfection, immunotherapy could control low bacterial loads with as little as 20 % efficacy, but more effective drugs would be necessary for high bacterial loads. Antibiotics targeting bacterial replication and administered 10 h after infection would require 100 % efficacy, which could be reduced to 40 % with prophylaxis. Combining immunotherapy with antibiotics could substantially increase treatment success. Taken together, the results suggest when and why some therapies fail, determine the efficacy needed for successful treatment, identify potential immune effects, and show how the regulation of underlying mechanisms can be used to design new therapeutic strategies.
Model is encoded by Ruby and submitted to BioModels by Ahmad Zyoud
2020-04-02 | MODEL1812040005 | BioModels
Project description:Bronchial epithelial cells represent the first line of defense against invading airborne pathogens. They are important contributors to innate mucosal immunity and provide a variety of anti-microbial effectors. To investigate the role of epithelial cells upon infection of airway pathogens, we stimulated BEAS-2B cells for 4 h with UV-inactivated bronchial pathogens including Staphylococcus aureus, Pseudomonas aeruginosa and Respiratory Syncitial Virus (RSV) that among other receptors can strongly activate TLR2, TLR4 and TLR3, respectively. Keywords: expression profiling, response to pathogens
2007-02-27 | GSE6802 | GEO
Project description:Epithelial cells are the first point of contact for bacteria entering the respiratory tract. Streptococcus pneumoniae is an obligatory human pathobiont of the nasal mucosa, carried asymptomatically but also the cause of severe pneumoniae. The role of the epithelium in maintaining homeostatic interactions or mounting an inflammatory response to invasive S. pneumoniae is currently poorly understood. However, studies have shown that chromatin modifications, at the histone level, induced by bacterial pathogens interfere with the host transcriptional program and promote infection. In this study, we demonstrate that S. pneumoniae actively induces di-methylation of histone H3 on lysine 4 (H3K4me2), which persists for at least 9 days upon clearance of bacteria with antibiotics. We show that infection establishes a unique epigenetic program affecting the transcriptional response of epithelial cells, rendering them more permissive upon secondary infection. Our results establish H3K4me2 as a unique modification induced by infection, distinct from H3K4me3, which localizes to enhancer regions genome-wide. Therefore, this study reveals evidence that bacterial infection leaves a memory in epithelial cells after bacterial clearance, in an epigenomic mark, thereby altering cellular responses for subsequent infections.
2024-05-17 | GSE230141 | GEO
Project description:Fire blight (FB) is a bacterial disease affecting plants from Rosaceae family, including apple and pear. FB develops after the infection of Erwinia amylovora, gram-negative enterobacterium, and results in burnt-like damages and wilting, which can affect all organs of the plant. Although the mechanisms underlying disease response in apples are not elucidated yet, it has been well described that FB resistance depends on the rootstock type. The main objective of this work was to identify miRNAs involved in response to bacterial infection in order to better explain apple defense mechanisms against fire blight disease. We performed deep sequencing of eighteen small RNA libraries obtained from inoculated and non-inoculated Gala apple leaves. 233 novel plant mature miRNAs were identified together with their targets and potential role in response to bacterial infection. We identify three apple miRNAs responding to inoculation (mdm-miR168a,b, mdm-miR194C and mdm-miR1392C) as well as miRNAs reacting to bacterial infection in a rootstock-specific manner (miR395 family). Our results provide insights into the mechanisms of fire blight resistance in apple.
2016-08-28 | GSE72346 | GEO
Project description:Deciphering the rapid expression and the underlying mechanisms of antibacterial effectors is critical to host defense against bacterial infection. Bacterial infection can reprogram cellular metabolism, however, the immunometabolism and its cross-talk with epigenetics in the regulation of antibacterial innate immunity remain to be fully understood. Here we report that nuclear hnRNPA2B1 is required to antibacterial innate response by promoting Il1b transcription. Myeloid-specific Hnrnpa2b1-deficient mice are susceptible to bacterial infection, resulting from IL-1β production insufficiency. The screenings identify the metabolite adenine in the nucleus to be able to bind and activate hnRNPA2B1. Adenine directly recruits hnRNPA2B1 to Il1b enhancers for increasing chromatin accessibility to promote Il1b transcription through NCL and FTO-mediated DNA 6mA demethylation of Il1b gene enhancers. Furthermore, bacterial infection elevates nuclear adenine levels, and in vivo administration of adenine protects mice from bacterial infection through hnRNPA2B1-IL1 circuit. Our findings provide an undiscovered paradigm of cross-regulation between epigenetic and metabolic pathways in antibacterial innate immunity, adding insight and proposing new approach to the treatment of bacterial infections.
2025-04-28 | GSE263373 | GEO