Abstract
Pseudomonas aeruginosa (Pa) is the leading cause of chronic lung infection in Cystic Fibrosis (CF) patients. It is well recognized that CF epithelial cells fail to develop an appropriate response to infection, allowing bacterial colonization and a chronic inflammatory response. Since long non-coding RNAs (lncRNAs), are known to play a key role in regulating mammalian innate immune response, we hypothesized that CF cells exposed to Pa could express a specific lncRNA signature responsible of the maladaptative CF response. We analyzed transcriptomic datasets to compare the expression profiles of lncRNAs in primary CF and non-CF epithelial cells infected with Pa at 0, 2, 4, and 6 h of infection. Our analysis identified temporal expression signatures of 25, 73, 15, and 26 lncRNA transcripts differentially expressed at 0, 2, 4, and 6 h post-infection respectively, between CF and non-CF cells. In addition, we identified profiles specific to CF and non-CF cells. The differential expression of two candidate lncRNAs were independently validated using real-time PCR. We identified a specific CF signature of lncRNA expression in a context of Pa infection that could potentially play a role in the maladaptive immune response of CF patients.
Highlights
Cystic fibrosis (CF) is an autosomal recessive genetic disorder affecting one in 3,500 live births, in Caucasian populations
The data were generated from human bronchial epithelial cells from four CF patients homozygous for the p.F508del mutation and four healthy donors, each infected with Pseudomonas aeruginosa (Pa) at 0.25 Multiplicity of Infection (MOI) for 0, 2, 4, and 6 h
For identifying differentially expressed genes and transcripts in CF compared to non-CF epithelial cells, we used cuffdiff and the reference gene and transcript annotations from the GENCODE version 23 for guiding the assembly
Summary
Cystic fibrosis (CF) is an autosomal recessive genetic disorder affecting one in 3,500 live births, in Caucasian populations. A deficient CFTR results in excessive secretion of abnormally thick and viscous mucus with impairment of innate immune host defenses This results in chronic infection and inflammation, which together acts to further deteriorate the lung function (Palmer and Whiteley, 2015). The current strongest evidence supports their role in cancer (Tsai et al, 2011), lncRNAs play key roles in regulating mammalian innate immune responses as well (Sigdel et al, 2015) Depending on their localization, they act on gene expression through interactions with DNA, RNA or proteins (Rinn and Chang, 2012) through various mechanisms including chromatin remodeling, epigenetic regulation, transcription, mRNA splicing, RNA decay and enhancer functions (Li et al, 2016). We re-analyzed the RNA-seq data with this perspective and evaluated the expression profiles of lncRNAs in infected CF and nonCF epithelial cells at the aim of identifying a specific CF signature for lncRNA expression in the presence of Pa infection
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