Similar Datasets
Project description:Pilot study of transcriptomic responses to IL13 and HRV-A and their interaction
| PRJNA667927 | ENA
Project description:We report the application of RNA sequencing technology for high-throughput profiling of gene expression responses to human rhinovirus infection at 24 hours in air-liquid interface human airway epithelial cell cultures derived from 6 asthmatic and 6 non-asthmatic donors. RNA-seq analysis identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1), and novel ones that were identified for the first time in this study (e.g. CCRL1, CDHR3). We concluded that air liquid interface cultured human airway epithelial cells challenged with live HRV are a useful in vitro model for the study of rhinovirus induced asthma exacerbation, given that our findings are consistent with clinical data sets. Furthermore, our data suggest that abnormal airway epithelial structure and inflammatory signaling are important contributors to viral induced asthma exacerbation. Differentiated air-liquid interface cultured human airway epithelial cell mRNA profiles from 6 asthmatic and 6 non-asthmatic donors after 24 hour treatment with either HRV or vehicle control were generated by deep sequencing, using Illumina HiSeq 2000.
2015-03-01 | E-GEOD-61141 | biostudies-arrayexpress
Project description:The lack of a robust system to reproducibly propagate HRV-C substantially hampered our understanding of the common respiratory virus. We sought to develop an organoid-based system to reproducibly propagate HRV-C and characterize virus-host interaction using the respiratory organoids established by our team. We demonstrated that airway organoids sustained serial virus passage with the aid of CYT-387-mediated immunosuppression; nasal organoids, an organoid model more closely simulating the human upper airway, achieved this without any intervention. Nasal organoids were more susceptible to HRV-C than airway organoids. Intriguingly, we observed a more intensive innate immune response in airway organoids than nasal organoids upon HRV-C infection, which was reproduced in a Poly (I:C) stimulation assay. Treatment with an anti-CDHR3 and two antivirals significantly reduced HRV-C viral growth in nasal organoids. An organoid-based immunofluorescence assay was established to titrate HRV-C infectious particles. Collectively, we developed an organoid-based system to reproducibly propagate the previously uncultivable HRV-C, which enabled an in-depth elucidation of HRV-C infection and innate immunity unprecedentedly. The organoid-based HRV-C infection model can be extended for developing antiviral strategies. More importantly, our study has paved a new avenue for propagating and studying other uncultivable human and animal viruses.
2024-11-18 | GSE254400 | GEO
Project description:Human rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in humans and highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examined the links between viral host defense, cellular metabolism, and epithelial barrier function. We observed that early HRV-C15 infection induced a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induced ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1alpha regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.
2021-04-30 | PXD024591 | Pride
Project description:Rationale: Mast cells (MCs) within the airway epithelium in asthma are closely related to airway dysfunction, but crosstalk between airway epithelial cells (AECs) and MCs in asthma remains incompletely understood. Human rhinovirus (HRV) infections are key triggers for asthma progression and AECs from individuals with asthma may have dysregulated anti-viral responses. Objectives: We utilize primary phenotyped AECs in an ex vivo coculture model system to examine crosstalk between AECs and MCs following epithelial HRV infection. Methods: Primary AECs were obtained from children with asthma (n=11) and healthy children (n=10), differentiated at air-liquid interface, and cultured in the presence of laboratory of allergic diseases-2 (LAD2) MCs. AECs were infected with HRV serogroup A 16 (HRV16) for 48 hours. RNA isolated from both AECs and MCs underwent RNA-sequencing (RNAseq) analysis. Direct effects of epithelial-derived interferons on LAD2 MCs were examined by qPCR. Results: MCs increased expression of pro-inflammatory and anti-viral genes in AECs. AECs demonstrated a robust antiviral response following HRV16 infection that resulted in significant changes in MC gene expression, including upregulation of genes involved in anti-viral responses, leukocyte activation, and type-2 (T2) inflammation. Subsequent ex vivo modeling demonstrated that IFN-β induces MC IL13 expression. The effects of AEC phenotype were small relative to the effects of viral infection and the presence of MCs. Conclusions: There is significant crosstalk between AECs and MCs, which are present in the epithelium in asthma. Epithelial-derived interferons not only play a role in viral suppression, but further alter MC immune responses including specific T2 genes.
2022-06-22 | GSE206680 | GEO
Project description:Human Rhinovirus (HRV) infection can trigger exacerbations of asthma. Understanding of the mechanisms provoking airway inflammation and remodeling in asthma, as well as the pathogenic mechanisms of HRV infection and its association with asthma exacerbations, may offer significant opportunities for improved disease management. Genome-wide expression analysis of HRV type 1A-infected primary bronchial epithelial (PBE) cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of gene expression after HRV infection in vitro. Keywords: response to rhinovirus infection
2008-11-01 | GSE13396 | GEO
Project description:We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.
2017-06-29 | GSE87463 | GEO
Project description:Human Rhinovirus (HRV) infection can trigger exacerbations of asthma. Understanding of the mechanisms provoking airway inflammation and remodeling in asthma, as well as the pathogenic mechanisms of HRV infection and its association with asthma exacerbations, may offer significant opportunities for improved disease management. Genome-wide expression analysis of HRV type 1A-infected primary bronchial epithelial (PBE) cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of gene expression after HRV infection in vitro. Experiment Overall Design: Frozen stocks of human PBE cells obtained from the bronchial brushings of six normal and five asthmatic individuals were grown in vitro in Bronchial Epithelial Growth Media (BEGM, Lonza). Subconfluent monolayers of PBE cells were infected with purified and concentrated minor group HRV serotype 1A at multiplicity of infection of 10 plaque forming units (pfu) per cell or mock-infected with growth media alone. Cells were lysed 16 hours post infection (p.i.) and isolated total RNAs were analyzed using the Human Genome U133 Plus 2.0 GeneChip arrays (Affymetrix, Santa Clara, CA).
2008-11-13 | E-GEOD-13396 | biostudies-arrayexpress
Project description:We report the application of RNA sequencing technology for high-throughput profiling of gene expression responses to human rhinovirus infection at 24 hours in air-liquid interface human airway epithelial cell cultures derived from 6 asthmatic and 6 non-asthmatic donors. RNA-seq analysis identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1), and novel ones that were identified for the first time in this study (e.g. CCRL1, CDHR3). We concluded that air liquid interface cultured human airway epithelial cells challenged with live HRV are a useful in vitro model for the study of rhinovirus induced asthma exacerbation, given that our findings are consistent with clinical data sets. Furthermore, our data suggest that abnormal airway epithelial structure and inflammatory signaling are important contributors to viral induced asthma exacerbation.
2015-03-01 | GSE61141 | GEO
Project description:Idiopathic pulmonary arterial hypertension (IPAH) is characterized by medial hypertrophy due to pulmonary arterial smooth muscle cell (paSMC) hyperplasia. Interleukin (IL)-13 is a potent regulator of tissue fibrosis and remodelling, and its effects are dependent on the cell-type specific expression of the IL-13 receptor isotypes IL-4Rα, IL-13Rα1, and IL-13Rα2. In order to identify the possible mechanism how IL-13 can exert its antiproliferative effect on paSMC microarray analysis was performed. For this purpose paSMC were stimulated with IL-13(10ng/ml) for 2h and 6h, respectively and subjected to microarray analysis.
2010-04-17 | GSE15739 | GEO