Abstract
BackgroundThe epithelium is the first line of defense against pathogens. Notably the epithelial cells lining the respiratory track are crucial in sensing airborne microbes and mounting an effective immune response via the expression of target genes such as cytokines and chemokines. Gene expression regulation following microbial recognition is partly regulated by chromatin re-organization and has been described in immune cells but data from epithelial cells is not as detailed. Here, we report genome-wide changes of the H3K27ac mark, characteristic of activated enhancers and promoters, after stimulation of nasopharyngeal epithelial cells with the bacterial endotoxin Lipopolysaccharide (LPS).ResultsIn this study, we have identified 626 regions where the H3K27ac mark showed reproducible increase following LPS induction in epithelial cells. This indicated that sensing of LPS led to opening of the chromatin in our system. Moreover, this phenomenon seemed to happen extensively at enhancers regions and we could observe instances of Super-enhancer formation. As expected, LPS-increased H3K27ac regions were found in the vicinity of genes relevant for LPS response and these changes correlated with up-regulation of their expression. In addition, we found the induction of H3K27ac mark to overlap with the binding of one of the NF-kB members and key regulator of the innate immune response, RELA, following LPS sensing. Indeed, inhibiting the NF-kB pathway abolished the deposition of H3K27ac at the TNF locus, a target of RELA, suggesting that these two phenomena are associated.ConclusionsEnhancers’ selection and activation following microbial or inflammatory stimuli has been described previously and shown to be mediated via the NF-kB pathway. Here, we demonstrate that this is also likely to occur in the case of LPS-sensing by nasopharyngeal epithelial cells as well. In addition to validating previous findings, we generated a valuable data set relevant to the host immune response to epithelial cell colonizing or infecting pathogens.
Highlights
The epithelium is the first line of defense against pathogens
In order to investigate changes in chromatin after LPS sensing by epithelial cells, we performed ChIP-seq experiments for Histone 3 Lysine acetylation (H3K27ac) with or without treatment, in Detroit 562 cells
Differential binding analysis allowed us to determine LPS-induced changes in H3K27ac. 626 peaks were identified as LPS-increased – peaks for which the signal after LPS stimulation was higher compared to the control – in both ChIP-seq replicates (Group 1) while other groups of peaks showed less reproducible changes (Groups 2, 3 and 4) (Fig. 1b)
Summary
The epithelial cells lining the respiratory track are crucial in sensing airborne microbes and mounting an effective immune response via the expression of target genes such as cytokines and chemokines. Epithelial cells are the first to detect microbes and are crucial in mounting an effective innate immune response as well as interacting with more. These cells recognize specific microbial components through pattern recognition receptors, mainly Toll-like receptors (TLR) [3]. Selection of regulatory regions, enhancers, following stimulation consists of interplay between lineage-determining and signaldependent transcription factors that together achieve specific cell response to a particular stimulus [5]
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