Communication Dans Un Congrès Année : 2021

Role of HDAC in the mechanism of infection of intestinal epithelial cells by adherent-invasive Escherichia coli bacteria isolated from patients with Crohn’s disease

Résumé

Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract evolving in a relapsing and remitting manner. A particular pathotype of Escherichia coli abnormally colonizes the intestinal mucosa of CD patients, the adherent-invasive Escherichia coli (AIEC), and most of the studies performed on AIEC support their involvement in the etiology of CD. However, others factors such as epigenetic modifications seem to be involved in the pathogenesis of CD. Epigenetic alterations have been observed in patients such as a global lower expression of the enzymes involved in the deacetylation of histones, the histone deacetylases (HDAC). Based on these data, we aimed to investigate the role of HDAC in the mechanism of infection of intestinal epithelial cells (IECs) by AIEC through the study of (1) the role of HDAC in the invasion process of the host cell by AIEC and by examining (2) the role of HDAC in the establishment of the inflammatory response during AIEC infection of IECs. Chemical inhibition of HDAC and silencing of the different HDAC allowed us to show that HDAC1 limits the invasion of cells by the AIEC LF82 strain whereas HDAC5 favors it. Following a RNA-seq analysis, we identified HDAC1--regulated genes and focused further experiments on EMP2 gene. Specific silencing of EMP2 in IECs revealed that EMP2 silencing decreased the invasion ability of AIEC suggesting that EMP2 could represent a potential therapeutic target to limit AIEC colonization. We also identified deregulated genes following the infection of IECs by the AIEC LF82 strain, most of them being involved in the inflammatory response. The study of the expression level of these genes in cells silenced for HDAC1 and HDAC3 resulted in the observation that HDAC1 limits the expression of these pro-inflammatory genes unlike HDAC3 which promotes their expression. To conclude, EMP2 and HDAC3 could represent two interesting therapeutic targets to limit AIEC invasion of IECs and inflammatory response, respectively.

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Dates et versions

hal-04977418 , version 1 (05-03-2025)

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  • HAL Id : hal-04977418 , version 1

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Mélissa Chervy, Nicolas Barnich, Jérémy Denizot. Role of HDAC in the mechanism of infection of intestinal epithelial cells by adherent-invasive Escherichia coli bacteria isolated from patients with Crohn’s disease. Journées de l'Ecole doctorale SVSAE 2021, Jun 2021, Clermont-ferrand, France. ⟨hal-04977418⟩
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