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:Multicenter surveillance study of lower respiratory tract infections
Project description:This series includes 278 microarrays used to detect respiratory viruses in a set of nasopharyngeal lavage specimens from children with respiratory tract infections Objective: To assess the utility of a pan-viral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections. Study Design: The Virochip was compared to conventional clinical direct fluorescent antibody (DFA) and PCR-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children. Results: The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity 85-90%, specificity 99%, PPV 94-96%, NPV 97-98%) in the detection of respiratory syncytial virus, influenza A, and rhino-/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect. Conclusions: Given its favorable sensitivity and specificity profile and greatly expanded spectrum of detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric respiratory tract infections. Keywords: viral detection The series includes 278 clinical specimens
Project description:<p>Accurate tests for microbiologic diagnosis of lower respiratory tract infections (LRTI) are needed. Gene expression profiling of whole blood represents a powerful new approach for analysis of the host response during respiratory infection that can be used to supplement pathogen detection testing. Using qPCR, we prospectively validated the differential expression of 10 genes previously shown to discriminate bacterial and non-bacterial LRTI confirming the utility of this approach. In addition, a novel approach using RNAseq analysis identified 141 genes differentially expressed in LRTI subjects with bacterial infection. Using "pathway-informed" dimension reduction, we identified a novel 11 gene set (selected from lymphocyte, α-linoleic acid metabolism, and IGF regulation pathways) and demonstrated a predictive accuracy for bacterial LRTI (nested CV-AUC=0.87). RNAseq represents a new and an unbiased tool to evaluate host gene expression for the diagnosis of LRTI.</p>
Project description:This series includes 278 microarrays used to detect respiratory viruses in a set of nasopharyngeal lavage specimens from children with respiratory tract infections Objective: To assess the utility of a pan-viral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections. Study Design: The Virochip was compared to conventional clinical direct fluorescent antibody (DFA) and PCR-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children. Results: The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity 85-90%, specificity 99%, PPV 94-96%, NPV 97-98%) in the detection of respiratory syncytial virus, influenza A, and rhino-/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect. Conclusions: Given its favorable sensitivity and specificity profile and greatly expanded spectrum of detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric respiratory tract infections. Keywords: viral detection
Project description:Bovine respiratory epithelial cells have different susceptibility to bovine
respiratory syncytial virus infection. The cells derived from the lower
respiratory tract were significantly more susceptible to the virus than those
derived from the upper respiratory tract. Pre-infection with virus of lower
respiratory tract with increased adherence of P. multocida; this was not the
case for upper tract. However, the molecular mechanisms of enhanced
bacterial adherence are not completely understood. To investigate whether
virus infection regulates the cellular adherence receptor on bovine trachea-,
bronchus- and lung-epithelial cells, we performed proteomic analyses.
Project description:Human metapneumovirus (HMPV) is a primary causative agent of acute lower respiratory tract infections. We used single cell RNA-sequencing (scRNA-seq) to assess lung immune profiles in a mouse model of HMPV infection.