In vitro evaluation of intestinal epithelial TLR activation in preventing food allergic responses

Sander de Kivit, Mary C. Tobin, Mark T. DeMeo, Susan Fox, Johan Garssen, Christopher B. Forsyth, Ali Keshavarzian, Alan L. Landay

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Alterations in the gut microbiota composition are associated with food allergy. Toll-like receptors (TLRs) respond to microbial stimuli. We studied the effects of the ligation of TLRs on intestinal epithelial cells (IECs) in preventing an allergic effector response. IEC monolayers (T84 cells) were co-cultured with CD3/28-activated PBMCs from healthy controls or atopic patients and simultaneously apically exposed to TLR2, TLR4 or TLR9 ligands. The barrier integrity of T84 cell monolayers was significantly reduced upon co-culture with PBMCs of food allergic subjects compared to healthy subjects. Apical exposure of IECs to a TLR9 ligand prevented PBMC-induced epithelial barrier disruption. Using PBMCs from food allergic subjects, apical TLR9 activation on IECs increased the IFN-γ/IL-13 and IL-10/IL-13 ratio, while suppressing pro-inflammatory IL-6, IL-8 and TNF-α production in an IEC-dependent manner. Hence, the activation of apical TLR9 on IECs, potentially by microbiota-derived signals, may play an important role in the prevention of allergic inflammation.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalClinical Immunology
Volume154
Issue number2
DOIs
StatePublished - Oct 2014
Externally publishedYes

Keywords

  • Cytokines;
  • Food allergy;
  • Intestinal epithelial cells;
  • PBMC;
  • Toll-like receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'In vitro evaluation of intestinal epithelial TLR activation in preventing food allergic responses'. Together they form a unique fingerprint.

Cite this