Distinct inflammatory and cytopathic characteristics of Escherichia coli isolates from inflammatory bowel disease patients

Stina Rikke Jensen, Hengameh Chloé Mirsepasi-Lauridsen, Anna Hammerich Thysen, Jørn Brynskov, Karen Angeliki Krogfelt, Andreas Munk Petersen, Anders Elm Pedersen, Susanne Brix

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    Abstract

    Escherichia coli (E. coli) may be implicated in the pathogenesis of inflammatory bowel disease (IBD), as implied from a higher prevalence of mucosa-associated E. coli in the gut of IBD-affected individuals. However, it is unclear whether different non-diarrheagenic E. coli spp. segregate from each other in their ability to promote intestinal inflammation. Herein we compared the inflammation-inducing properties of non-diarrheagenic LF82, 691-04A, E. coli Nissle 1917 (ECN) and eleven new intestinal isolates from different locations in five IBD patients and one healthy control. Viable E. coli were cultured with human monocyte-derived dendritic cells (moDCs) and monolayers of intestinal epithelial cells (IECs), followed by analysis of secreted cytokines, intracellular levels of reactive oxygen species and cellular death. The IBD-associated E. coli LF82 induced the same dose-dependent inflammatory cytokine profile as ECN and ten of the new E. coli isolates displayed as high level IL-12p70, IL-1β, IL-23 and TNF-α from moDCs irrespective of their site of isolation (ileum/colon/faeces), disease origin (diseased/non-diseased) or known virulence factors. Contrarily, 691-04A and one new IBD E. coli isolate induced a different cellular phenotype with enhanced killing of moDCs and IECs, coupled to elevated IL-18. The cytopathic nature of 691-04A and one other IBD E. coli isolate suggests that colonization with specific non-diarrheagenic E. coli could promote intestinal barrier leakage and profound intestinal inflammation, while LF82, ECN and the remaining non-diarrheagenic E. coli isolates hold notorious pro-inflammatory characteristics that can progress inflammation in case of intestinal barrier leakage.
    Original languageEnglish
    JournalInternational Journal of Medical Microbiology
    Volume305
    Issue number8
    Pages (from-to)925-936
    Number of pages12
    ISSN1438-4221
    DOIs
    Publication statusPublished - 2015

    Keywords

    • Cell death
    • Cytokine profile
    • Dendritic cells
    • IBD-associated E. coli
    • Inflammation

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