Volume 215, Issue 2 p. 135-144
Original Paper

Increased uptake of non-pathogenic E. coli via the follicle-associated epithelium in longstanding ileal Crohn's disease

ÅV Keita

ÅV Keita

Division of Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Sweden

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SY Salim

SY Salim

Division of Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Sweden

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T Jiang

T Jiang

Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Sweden

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P-C Yang

P-C Yang

Intestinal Disease Research Program, McMaster University, Hamilton, Canada

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L Franzén

L Franzén

Aleris Medilab, Täby, Sweden

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P Söderkvist

P Söderkvist

Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Sweden

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K-E Magnusson

K-E Magnusson

Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Sweden

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JD Söderholm

Corresponding Author

JD Söderholm

Division of Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Sweden

Division of Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Sweden.Search for more papers by this author
First published: 11 February 2008
Citations: 65

No conflicts of interest were declared.

Abstract

In Crohn's disease (CD), inflammation is driven by luminal commensal micro-organisms; however, mechanisms of early phases of inflammation need further clarification. The earliest observable lesions of recurrent CD are microscopic erosions at the specialized follicle-associated epithelium (FAE), which lines the Peyer's patches. Therefore, our aim was to investigate the mucosal barrier to non-pathogenic bacteria in FAE of CD. The FAE of macroscopically normal ileum from patients with longstanding CD, ulcerative colitis, and controls was studied in Ussing chambers regarding electrophysiology and permeability to 51Cr-EDTA, horseradish peroxidase, and non-pathogenic E. coli strains. Transepithelial passage routes and uptake into dendritic cells were studied by confocal and electron microscopy. FAE of CD showed increased numbers of adherent bacteria, after E. coli exposure in Ussing chambers, as well as spontaneously in non-exposed archival surgical tissues. Further, we found increased uptake of fluorescent E. coli K-12 and HB101 across FAE of CD, but not in ulcerative colitis. Microscopy demonstrated intercellular and transcellular uptake of E. coli in CD, but only transcellular in controls. FAE exposed to E. coli demonstrated changes in conductance and 51Cr-EDTA permeability, suggesting that bacteria affected the paracellular pathway in CD mucosa. Following bacterial uptake, CD mucosa also demonstrated an increased percentage of E. coli co-localizing with dendritic cells, and augmented tissue release of TNF-α. Our data present novel insights into the pathophysiology of CD by demonstrating a previously unrecognized defect of FAE barrier to bacteria in ileal CD, leading to increased load of commensal bacteria to the inductive sites of mucosal immunity. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.