A.fumigatus and the bronchial epithelium - A permissive relationship?

Gemma Hayes, Nicola Overton, Sara Gago, David Denning, Paul Bowyer

Abstract: 

Exome sequencing of individuals with aspergillosis demonstrates genetic variants that may impact on the structure/function of the respiratory epithelium and replication of these mutations, using CRISPR/Cas9 technology, results in morphological epithelial change. However, the transcriptional and translational response of the bronchial epithelium to Aspergillus fumigatus is poorly defined. Using a 16HBE cell line model, RNA-Seq and flow cytometry, we describe transcriptional and secretory epithelial responses to A. fumigatus at 6 hours post infection; assessing the inflammatory role of the bronchial epithelium in early host defence.

RNA-Seq data identified 11,022 differentially expressed genes with 457 having a p value of <0.05. Ingenuity pathway analysis® identified upregulation of pathways involved in cytoskeletal/cytoplasmic reorganisation and endocytosis, with enrichment of epithelial adherens junction and EGF signalling pathways. Regulation (up or down) of inflammatory pathways was notably absent; with only the chemokine CCL5 being present amongst the 457 differentially expressed genes. Flow cytometry cell supernatant analysis also failed to demonstrate an inflammatory response with undetectable levels of IL1β, IFNγ, IFNα, TNFα and IL10, 12p70, 18, 23 and 33 demonstrated. Elevated level of IL6, IL8 and CCL2 were seen, but with no significant difference between infected and control samples.

Rather than mounting an inflammatory response to A. fumigatus, transcriptional and flow cytometry data suggests a permissive, perhaps phagocytic, epithelial response raising the possibility of unchecked latent reservoirs of bronchial infection developing within the bronchial epithelium during the early phase of infection.

2016

abstract No: 

PA3971

Full conference title: 

European Respiratory Society 2016
    • ERS 26th (2016)