RNA-sequencing of PBMC cultured with PolyI:C or LPS, from a pediatric cohort who received OM85 or placebo.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE184487 | GEO | 2024/09/20
REPOSITORIES: GEO
Similar Datasets
Project description:<p><b>Public health importance</b>: Babies born preterm, approximately 1 out of every 9 live births in the United States, have significant respiratory morbidity over the first two years of life, exacerbated by respiratory viral infections. Many (<50%) return to pediatricians, emergency rooms and pulmonologists with symptoms of respiratory dysfunction (SRD): intermittent or chronic wheezing, poor growth and an excess of upper and lower respiratory tract infections (LRTI). SRD correlate inversely with gestational age and weight at birth and is more common in those with chronic lung disease of prematurity, yet its incidence and severity varies widely among both the prematurely born and those born at term. There is evidence from clinical studies and animal models that risks of LRTI and recurrent wheezing is influenced by gut and respiratory flora and by T cell responses to infection. Information gained from this study will be used to identify characteristics, risk factors and potential mechanisms for early and persistent lung disease in children born at term and born preterm.</p> <p>This Clinical Research Study will investigate the relationships between sequential respiratory viral infections, patterns of intestinal and respiratory bacterial colonization, and adaptive cellular immune phenotypes which are associated with increased susceptibility to respiratory infections and long term respiratory morbidity in preterm and full term infants. We hypothesize that the timing and acquisition of specific viral infections and bacterial species are directly related to respiratory morbidity in the first year of life as defined by SRD and by measures of pulmonary function. We hypothesize that cellular and molecular immuno-maturity are altered due to factors presented by premature birth in such a way as to promote chronic inflammatory and cytotoxic damage to the lung, with subsequent enhanced, damaging responses to infectious agents and environmental irritants. Our preliminary studies demonstrate both feasibility and expertise in mutiparameter immunophenotyping of small volume peripheral blood samples obtained from premature infants including gene expression arrays of flow cytometry sorted cells. We will use new technologies for known viral identification, as well as high-throughput metagenome sequencing of RNA and DNA virus like particles (VLP) to be used for viral discovery in infant respiratory sample and use of high-throughput pyrosequencing (454T) of bacterial 16S rRNA to determine shifts in bacterial community structure, occurring in pre-term (PT) as compared to full term (FT) infants, over the first year of life. Finally, we present statistical approaches to stratify disease risk predictors using multivariate logistic regression modeling approaches. We propose to evaluate T cell phenotypic and functional profiles relative to viral and predominant bacterial exposures according to highly complementary, but independent, Specific Objectives.</p> <p><b>Objective 1</b>: To determine if viral respiratory infections and patterns of respiratory and gut bacterial community structure (microbiome) in prematurely born babies predict the rate and degree of immunologic maturation, and pulmonary dysfunction, measured from birth to 36 weeks corrected gestational age (CGA).</p> <p><b>Objective 2</b>: To determine the relationship between respiratory viral infections and disease severity up to one year CGA, and the lymphocyte (Lc) phenotypes documented at term gestation (birth for term infants and 36 wks/NICU discharge in preterm infants) and at one year CGA. Three secondary outcomes of this objective will be to a) relate the quantity, type and severity of viral infections with pulmonary function at one and three years of life, b) relate the viral community structure to severity of viral infections and c) to seek evidence of modulation of viral susceptibility by bacterial respiratory and gut community structure (microbiome). The relationship of colonization with known and non-identified bacterial species in both the respiratory tract and the gut will be evaluated. </p>
| phs001347 | dbGaP
Project description:Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health-care burdens. Despite posing substantial health risks, airway immune responses in early life remain largely unexplored. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms. Using a trans-well pseudostratified nasal epithelial cell system, we examined age-dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches. Our studies revealed differences in innate-receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular networks for influenza A and respiratory syncytial virus, emphasizing highly relevant virus-specific pathways. This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers novel insights that should enable a deeper understanding of age-related differences in nasal epithelial cell immunity following respiratory virus infections.
2024-11-06 | PXD042209 | Pride
Project description:The use of microbiological cultures for diagnosing bacterial infections in young febrile infants have substantial limitations, including false positive and false negative cultures, and non-ideal turn-around times. Analysis of host genomic expression patterns (âRNA biosignaturesâ) in response to the presence of specific pathogens, however, may provide an alternate and potentially improved diagnostic approach. This study was designed to define bacterial and non-bacterial RNA biosignatures to distinguish these infections in young febrile infants. A total of 279 febrile infants and 19 healthy afebrile control infants aged 0-6 months (for a total of 298 samples) for microarray analysis. For analytic purposes, we classified patients into two groups, those with bacterial infections (n=89) and those with non-bacterial infections (n=190). 144 of the samples were run on Illumina HT12 V4 R1 chips. Of these, there were 34 bacterial infections, 105 non-bacterial infections, and 5 healthy afebrile controls. 154 of the samples were run on Illumina HT12 V4 R2 chips. Of these, there were 55 bacterial infections, 85 non-bacterial infections, and 14 healthy afebrile controls.
2016-07-27 | E-GEOD-64456 | biostudies-arrayexpress
Project description:Introduction: Thymic Stromal Lymphopoietin (TSLP) is a primarily epithelial-derived cytokine that drives type 2 allergic immune responses. Early life viral respiratory infections elicit high TSLP production, which leads to the development of type 2 inflammation and airway hyperreactivity. The goal of this study was to examine in vivo and in vitro the human airway epithelial responses leading to high TSLP production during viral respiratory infections in early infancy. Methods: A total of 129 infants (<1m – 24m, median age 10m) with severe viral respiratory infections were enrolled for in vivo (n=113), and in vitro studies (n=16). Infants were classified as “high TSLP” or “low TSLP” for values above or below the 50th percentile. High vs. low TSLP groups were compared in terms of type I-III IFN responses and production of chemokines promoting antiviral (CXCL10), neutrophilic (CXCL1, CXCL5, CXCL8), and type 2 responses (CCL11, CCL17, CCL22). Human infant airway epithelial cell (AEC) cultures were used to define the transcriptomic (RNAseq) profile leading to high vs. low TSLP responses in vitro. Results: Infants in the high TSLP group had greater in vivo type III IFN airway production (median type III IFN in high TSLP 183.2 pg/ml vs. 63.4 pg/ml in low TSLP group, p= 0.007) and increased in vitro type I-III IFN AEC responses after stimulation with a viral mimic (poly I:C). Our RNAseq data showed that infants in the high TSLP group had significant baseline upregulation of IFN signature genes (e.g., IFIT2, IFI6, MX1) and pro-inflammatory chemokine genes prior to viral mimic stimulation. Infants in the high TSLP group also showed a baseline AEC pro-inflammatory state characterized by increased production of all the chemokines assayed (e.g., CXCL10, CXCL8) in the absence of viral stimuli. Conclusion: High TSLP responses in the human infant airways are associated with pre-activated airway epithelial IFN antiviral immunity and increased baseline AEC production of pro-inflammatory chemokines. These findings present a new paradigm underlying the high production of TSLP in the human infant airway epithelium and shed light on the pathogenesis of viral respiratory illnesses during early infancy and beyond childhood.
2024-03-01 | GSE248828 | GEO
Project description:Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represent an alternative to identifying new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens which are nevertheless highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top ten signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here.
2017-03-01 | GSE88825 | GEO
Project description:Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O2) and infections. The underlying mechanisms are still poorly understood. The hypothesis of this study is that dysregulated macrophage activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants.
Cord blood samples of preterm infants (n=14) and term infants (n=19) as well as peripheral blood from healthy adults (n=17) were collected. Age-dependent differences in immune responses of monocyte-derived Mä from preterm infants were characterized and compared to term infants and adults after lipopolysaccharide (LPS) exposure.
| EGAS00001004974 | EGA
Project description:Viral respiratory infections are an important public health concern, due to their prevalence, transmissibility, and potential to cause serious disease. Disease severity is the product of several factors beyond the presence of the infectious agent, including specific host immune responses, host genetic makeup and bacterial co-infections. To understand these interactions within natural infections we designed a longitudinal cohort study actively surveilling 18 different respiratory viruses over the course of 19 months (2016-2018) in Manhattan, New York City. The cohort includes individuals related to daycare facilities, high school students and health care workers. We retrieved weekly epidemiological and clinical data and collected over 4,000 nasal swabs for molecular characterization from 214 participants. Transcriptomic data enabled the characterization of specific markers of immune response, the identification of signatures associated with symptom severity and bacterial co-infections. We created a computational resource to facilitate access to the data and visualization of analytical results.
2023-01-30 | GSE223679 | GEO
Project description:Infection by the Gram-negative bacterium Pseudomonas aeruginosa is common in hospitalized immunocompromised as well as immunocompetent ventilated patients and is often life-threatening because of resistance of the bacteria to antibiotics. This prompts the question whether the host’s immune system can be educated to combat this bacterium. Bacterial lipopolysaccharide (LPS) is known to promote host resistance to bacterial infections although an understanding of the underlying mechanism is lacking. Here we show that prior exposure to a single low dose of LPS protects mice from a lethal infection by P. aeruginosa. These mice displayed expansion of a neutrophil and an interstitial macrophage population that were barely detectable in mice that did not receive LPS prior to infection. Both cell populations were distinguishable from other immune cell populations by being enriched in gene sets that included phagocytosis- and cell-killing-associated genes. The cell killing gene set in the neutrophil population uniquely expressed Lgals3, which encodes the multifunctional antibacterial protein, galectin-3. Intravital imaging of neutrophils for bacterial phagocytosis, assessment of bacterial killing and neutrophil-associated galectin-3 protein levels together with use of galectin-3-deficient mice collectively highlight neutrophils and galectin-3 as central players in LPS-mediated protection. Interrogating the relevance of these findings in hospitalized patients with acute respiratory failure revealed significantly higher galectin-3 levels in endotracheal aspirates (ETAs) of survivors compared to non-survivors, galectin-3 levels strongly correlating with a neutrophil signature in the ETAs. Taken together, our study provides impetus to harnessing the potential of galectin-3-expressing neutrophils to protect the lung from lethal infections and respiratory failure.
2024-04-15 | GSE237646 | GEO
Project description:Viral infections facilitate bacterial trafficking to the lower respiratory tract resulting in bacterial viral co infections. Bacterial dissemination to the lower respiratory tract is enhanced by influenza A virus induced epithelial cell damage and dysregulation of immune responses. Epithelial cells act as the first line of defense and detect pathogens by a high variety of pattern recognition receptors. The post translational modification ubiquitin is involved in almost every cellular process. Moreover, ubiquitination contributes to the regulation of host immune responses, influenza A virus uncoating and transport within host cells. We applied proteomics with a special focus on ubiquitination to assess the impact of single bacterial and viral as well as bacterial viral co-infections on bronchial epithelial cells. We used Tandem Ubiquitin Binding Entities to enrich polyubiquitinated proteins and assess changes in the ubiquitinome. Infecting 16HBE cells with Streptococcus pyogenes led to an increased abundance of proteins related to mitochondrial translation and energy metabolism in proteome and ubiquitinome. In contrast, influenza A virus infection mainly altered the ubiquitinome. Co-infections had no additional impact on protein abundances or affected pathways. Changes in protein abundance and enriched pathways were assigned to imprints of both infecting pathogens.
2022-02-24 | PXD025146 | Pride
Project description:The use of microbiological cultures for diagnosing bacterial infections in young febrile infants have substantial limitations, including false positive and false negative cultures, and non-ideal turn-around times. Analysis of host genomic expression patterns (“RNA biosignatures”) in response to the presence of specific pathogens, however, may provide an alternate and potentially improved diagnostic approach. This study was designed to define bacterial and non-bacterial RNA biosignatures to distinguish these infections in young febrile infants.
2016-07-27 | GSE64456 | GEO