Original ResearchFull Report: Basic and Translational—Alimentary TractCrohn's Disease–Associated Adherent Invasive Escherichia coli Modulate Levels of microRNAs in Intestinal Epithelial Cells to Reduce Autophagy
Section snippets
Materials and Methods
Information on bacterial strains, human tissue samples, cell culture, invasion assays, miRNAs, plasmid construction, in vitro transfection and luciferase assay, protein extraction and Western blot analysis, RNA extraction and quantitative reverse-transcription polymerase chain reaction (qRT-PCR), miRNA target prediction, fluorescent microscopy, intestinal epithelial cell (IEC) isolation, chromatin immunoprecipitation assay, and enzyme-linked immunosorbent assay appears in the Supplementary
Identification of CD-Associated miRNAs That Are Dysregulated by AIEC Infection
To discover the CD-associated miRNAs involved in host response to AIEC infection, we analyzed miRNA expression in human intestinal epithelial T84 cells infected with the AIEC reference strain LF82 by qRT-PCR. Among the CD-associated miRNAs previously reported,19 expression of homo sapiens (hsa)-miR-30c and hsa-miR-130a was up-regulated significantly by infection with LF82 but not with the nonpathogenic E coli K12 MG1655 or the commensal E coli HS strain (Figure 1A). Infection with other
Discussion
The potential role of autophagy in CD onset has been highlighted with the identification of genetic risk polymorphisms in various autophagy-related genes and those that regulate autophagy. Exciting recent progress has been made in understanding the mechanistic links between defects in autophagy-mediated bacterial handling, innate immune activation, and CD pathogenesis. Among the infectious factors that have been shown to be involved in the dysregulated immune response observed in CD, much
Acknowledgments
The authors thank the Imagerie Confocale Clermont-Ferrand (ICCF) platform (IFR79 Santé Université d'Auvergne, Clermont-Ferrand, France) for confocal microscopy, Dr Pierre Lapaquette and Professor Richard Bonnet for valuable discussions, and Dr Emilie Vazeille and Dr Nicolas Barnich for help with human biopsy samples and the CEABAC10 transgenic mice.
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Conflicts of interest The authors disclose no conflicts.
Funding This work was supported by the Ministère de la Recherche et de la Technologie, Inserm (UMR1071), INRA (USC-2018), and by grants from the Association François Aupetit (A.D.M.), the European Union FP7 People Marie Curie International Incoming Fellowship (H.N.) and Région Auvergne (Nouveau Chercheur to G.D.).
Author names in bold designate shared co-first authorship.