Flagellin induces β-defensin 2 in human colonic ex vivo infection with enterohemorrhagic Escherichia coli

Lewis, Steven, Prior, Alison, Ellis, Samuel, Cook, Vivienne, Chan, Simon, Gelson, William and Schuller, Stephanie (2016) Flagellin induces β-defensin 2 in human colonic ex vivo infection with enterohemorrhagic Escherichia coli. Frontiers in Cellular and Infection Microbiology, 6. ISSN 2235-2988

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Abstract

Enterohemorrhagic E. coli (EHEC) is an important foodborne pathogen in the developed world and can cause life-threatening disease particularly in children. EHEC persists in the human gut by adhering intimately to colonic epithelium and forming characteristic attaching/effacing lesions. In this study, we investigated the innate immune response to EHEC infection with particular focus on antimicrobial peptide and protein expression by colonic epithelium. Using a novel human colonic biopsy model and polarized T84 colon carcinoma cells, we found that EHEC infection induced expression of human β-defensin 2 (hBD2), whereas hBD1, hBD3, LL-37 and lysozyme remained unchanged. Infection with specific EHEC deletion mutants demonstrated that this was dependent on flagellin, and apical exposure to purified flagellin was sufficient to stimulate hBD2 and also interleukin (IL)-8 expression ex vivo and in vitro. Flagellin-mediated hBD2 induction was significantly reduced by inhibitors of NF-κB, MAP kinase p38 and JNK but not ERK1/2. Interestingly, IL-8 secretion by polarized T84 cells was vectorial depending on the side of stimulation, and apical exposure to EHEC or flagellin resulted in apical IL-8 release. Our results demonstrate that EHEC only induces a modest immune response in human colonic epithelium characterized by flagellin-dependent induction of hBD2 and low levels of IL-8.

Item Type: Article
Additional Information: © 2016 Lewis, Prior, Ellis, Cook, Chan, Gelson and Schüller. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Uncontrolled Keywords: ehec,colonic epithelium,innate immune response,defensin,interleukin-8,flagellin
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 14 Jun 2016 11:00
Last Modified: 22 Apr 2020 01:28
URI: https://ueaeprints.uea.ac.uk/id/eprint/59318
DOI: 10.3389/fcimb.2016.00068

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