Peanut allergens alter intestinal barrier permeability and tight junction localisation in Caco-2 cell cultures

Cell Physiol Biochem. 2014;33(6):1758-77. doi: 10.1159/000362956. Epub 2014 May 23.

Abstract

Background/aims: Allergen absorption by epithelia may play an important role in downstream immune responses. Transport mechanisms that can bypass Peyer's patches include transcellular and paracellular transport. The capacity of an allergen to cross via these means can modulate downstream processing of the allergen by the immune system. The aim of this study was to investigate allergen-epithelial interactions of peanut allergens with the human intestinal epithelium.

Methods: We achieved this using the human Caco-2 cell culture model, exposed to crude peanut extract. Western and immunofluorescence analysis were used to identify the cellular and molecular changes of peanut extract on the intestinal epithelium.

Results: Following exposure of Caco-2 cells to peanut extract, binding of the peanut allergens Ara h 1 and Ara h 2 to the apical cellular membrane and transcytosis across the monolayers were observed. Additionally, the co-localisation of the transmembrane tight junction proteins occludin, JAM-A and claudin-1, with the intracellular adhesion protein ZO-1 was modified.

Conclusion: Disruption of Caco-2 barrier integrity through tight junction disruption may enable movement of peanut proteins across the intestinal epithelium. This accounts for peanut's increased allergenicity, compared to other food allergens, and provides an explanation for the potency of peanut allergens in immune response elicitation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2S Albumins, Plant / metabolism
  • Allergens / metabolism
  • Antigens, Plant / metabolism
  • Arachis / chemistry*
  • Biological Transport
  • Blotting, Western
  • Caco-2 Cells
  • Cell Adhesion Molecules / metabolism
  • Cell Survival / drug effects
  • Claudin-1 / metabolism
  • Glycoproteins / metabolism
  • Humans
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Membrane Proteins
  • Microscopy, Confocal
  • Models, Biological
  • Occludin / metabolism
  • Permeability / drug effects
  • Plant Extracts / metabolism
  • Plant Extracts / pharmacology*
  • Plant Proteins / metabolism
  • Protein Binding
  • Receptors, Cell Surface / metabolism
  • Tight Junctions / drug effects*
  • Tight Junctions / metabolism
  • Zonula Occludens-1 Protein / metabolism

Substances

  • 2S Albumins, Plant
  • Allergens
  • Antigens, Plant
  • Ara h 1 protein, Arachis hypogaea
  • Ara h 2 allergen, Arachis hypogaea
  • Cell Adhesion Molecules
  • Claudin-1
  • F11R protein, human
  • Glycoproteins
  • Membrane Proteins
  • Occludin
  • Plant Extracts
  • Plant Proteins
  • Receptors, Cell Surface
  • TJP1 protein, human
  • Zonula Occludens-1 Protein