Larabi Anaïs, Salesse Laurène, Cordonnier Charlotte, Etienne-Mesmin Lucie, Barnich Nicolas, Dalmasso Guillaume, Nguyen Hang Thi Thu
M2iSH, UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 2018, CRNH, 63001 Clermont-Ferrand, France.
MEDIS, INRAE, Université Clermont Auvergne, 63001 Clermont-Ferrand, France.
Microorganisms. 2020 Aug 7;8(8):1205. doi: 10.3390/microorganisms8081205.
Adherent-invasive (AIEC), which abnormally colonize the ileal mucosa of Crohn's disease (CD) patients, are able to invade intestinal epithelial cells (IECs) and translocate through M cells overlying Peyer's patches. The levels of microRNA (miRNA) and gene expression in IECs and M cells upon AIEC infection have not been investigated. Here, we used human intestinal epithelial Caco-2 monolayers and an in vitro M-cell model of AIEC translocation to analyze comprehensive miRNA and gene profiling under basal condition and upon infection with the reference AIEC LF82 strain. Our results showed that AIEC LF82 translocated through M cells but not Caco-2 monolayers. Both differential gene expression and miRNA profile in M cells compared to Caco-2 cells were obtained. In addition, AIEC infection induces changes in gene and miRNA profiles in both Caco-2 and M cells. In silico analysis showed that certain genes dysregulated upon AIEC infection were potential targets of AIEC-dysregulated miRNAs, suggesting a miRNA-mediated regulation of gene expression during AIEC infection in Caco-2, as well as M cells. This study facilitates the discovery of M cell-specific and AIEC response-specific gene-miRNA signature and enhances the molecular understanding of M cell biology under basal condition and in response to infection with CD-associated AIEC.
黏附侵袭性大肠杆菌（AIEC）可异常定殖于克罗恩病（CD）患者的回肠黏膜，能够侵袭肠上皮细胞（IEC）并通过派尔集合淋巴结上方的M细胞进行转运。目前尚未研究AIEC感染后IEC和M细胞中微小RNA（miRNA）水平及基因表达情况。在此，我们使用人肠上皮Caco-2单层细胞和AIEC转运的体外M细胞模型，分析基础条件下以及感染参考AIEC LF82菌株后的综合miRNA和基因谱。我们的结果显示，AIEC LF82可通过M细胞而非Caco-2单层细胞进行转运。获得了与Caco-2细胞相比M细胞中的差异基因表达和miRNA谱。此外，AIEC感染可诱导Caco-2和M细胞中的基因和miRNA谱发生变化。计算机分析表明，AIEC感染后失调的某些基因是AIEC失调miRNA的潜在靶标，这表明在Caco-2以及M细胞的AIEC感染过程中存在miRNA介导的基因表达调控。本研究有助于发现M细胞特异性和AIEC反应特异性的基因-miRNA特征，并增强对基础条件下以及对与CD相关的AIEC感染作出反应时M细胞生物学的分子理解。
