Subversion of human intestinal mucosa innate immunity by a Crohn's disease-associated E. coli

Mucosal Immunol. 2015 May;8(3):572-81. doi: 10.1038/mi.2014.89. Epub 2014 Oct 1.


Adherent-invasive Escherichia coli (AIEC), associated with Crohn's disease, are likely candidate contributory factors in the disease. However, signaling pathways involved in human intestinal mucosa innate host response to AIEC remain unknown. Here we use a 3D model of human intestinal mucosa explant culture to explore the effects of the AIEC strain LF82 on two innate immunity platforms, i.e., the inflammasome through evaluation of caspase-1 status, and NFκB signaling. We showed that LF82 bacteria enter and survive within a few intestinal epithelial cells and macrophages, without altering the mucosa overall architecture. Although 4-h infection with a Salmonella strain caused crypt disorganization, caspase-1 activation, and mature IL-18 production, LF82 bacteria were unable to activate caspase-1 and induce IL-18 production. In parallel, LF82 bacteria activated NFκB signaling in epithelial cells through IκBα phosphorylation, NFκBp65 nuclear translocation, and TNFα secretion. In addition, NFκB activation was crucial for the maintenance of epithelial homeostasis upon LF82 infection. In conclusion, here we decipher at the whole-mucosa level the mechanisms of the LF82-induced subversion of innate immunity that, by maintaining host cell integrity, ensure intracellular bacteria survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 1 / genetics
  • Caspase 1 / immunology
  • Crohn Disease / genetics
  • Crohn Disease / immunology
  • Crohn Disease / microbiology*
  • Crohn Disease / pathology
  • Epithelial Cells / immunology*
  • Epithelial Cells / microbiology
  • Gene Expression Regulation
  • Humans
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / immunology
  • Immune Evasion*
  • Immunity, Innate*
  • Immunity, Mucosal
  • Inflammasomes / immunology
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Macrophages / immunology*
  • Macrophages / microbiology
  • NF-KappaB Inhibitor alpha
  • Phosphorylation
  • Salmonella / immunology*
  • Signal Transduction
  • Tissue Culture Techniques
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology


  • I-kappa B Proteins
  • IL18 protein, human
  • Inflammasomes
  • Interleukin-18
  • NFKBIA protein, human
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Caspase 1