Steven B. Lewis, Alison Prior, Samuel J. Ellis, Vivienne Cook, Simon S. M. Chan, William Gelson, Stephanie Schüller
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.
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 March 2019.
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#7,427,924
of 22,879,161 outputs
Outputs from Frontiers in Cellular and Infection Microbiology
#1,591
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Outputs of similar age
#123,466
of 353,105 outputs
Outputs of similar age from Frontiers in Cellular and Infection Microbiology
#7
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Altmetric has tracked 22,879,161 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 6,437 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.3. This one has gotten more attention than average, scoring higher than 74% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 353,105 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
