Host-Specific Effects on Bacterial Modulation of Respiratory Epithelial Gene Expression and Alternative Splicing

Given the extensive variability inherent to humans and how variable microbiome composition is between individuals, we wanted to investigate inter-individual differences in host response to microbial colonization. Using primary normal human bronchial epithelial cells from six different adult donors (including both males and females and spanning in age from mid-20s to mid-50s), we cultivated air-liquid interface tissue cultures (ALI) from each donor. ALIs are pseudostratified cell cultures where the epithelial cells have differentiated into the appropriate subtypes (goblet cells, ciliated cells, club cells, etc). We colonized the ALI with one of three phylogenetically diverse microbes (Staphylococcus epidermidis, Rothia aeria, and Klebsiella aerogenes) for 12, 24, and 48 hours. At each time point, we sequenced the total RNA from the eukaryotic respiratory epithelial cells with the goal of identifying patterns of the gene expression change that were consistent or variable across the donors and evaluate if these patterns were dependent on the colonizing microbe. ]]>