WS10.4 Transcriptomic analysis of normal and cystic fibrosis human bronchial epithelial cells infected with Pseudomonas aeruginosa reveals distinct gene activation

Abstract

Objectives Cystic fibrosis (CF) is characterized by airway colonization by Pseudomonas aeruginosa ( P.a ) resulting in a prolonged inflammatory response. Here, we performed transcriptomic analysis of P.a -infected primary bronchial epithelial cells from non-CF and CF patients to look for new leads explaining P.a persistence in lungs in spite of a strong inflammatory response. Methods Non-CF and CF cells were infected by P.a at 0.25 MOI for 0, 2, 4 and 6 hours. Biological samples (4 CF and 4 non-CF) were processed for mRNA profiling using Illumina mRNA sequencing. Statistical analysis provided lists of genes having a significant differential expression (p Results We found 310, 295, 252 and 448 genes differentially down-regulated and 541, 343, 415, 532 differentially up-regulated in CF vs non-CF cells at 0, 2, 4 and 6 hours of infection, respectively. We identified genes that could explain the intense inflammatory response, the development of chronic infection or the absence of antiinflammatory response. Several genes such as IL-6, IL-17C, KLF2, TLR4, SLPI or GSTT1 were already known to play a role in the epithelium- P.a interaction but interestingly some genes were never or sparsely described in the lung CF disease. Conclusion Different clinical approaches are used to eliminate P.a especially antibiotic prescriptions, but none of them leading to complete eradication. Here, we identified mRNA pattern associated with P.a infection that could explain the lack of P.a eradication in CF. Those results may be the first step to study the development of new diagnostic tools and therapeutic strategies.