The effects of oral and enteric Campylobacter concisus strains on expression of TLR4, MD-2, TLR2, TLR5 and COX-2 in HT-29 cells.

Yazan Ismail,Stephen M Riordan,Li Zhang,Michael C Grimm,Hoyul Lee,Markus M. Heimesaat

doi:10.1371/journal.pone.0056888

Yazan Ismail, Stephen M Riordan + Show 4 more

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https://doi.org/10.1371/journal.pone.0056888

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Journal: PloS one	Publication Date: Feb 20, 2013
Citations: 69	License type: CC BY 4.0

Affiliation: UNSW Sydney, Prince of Wales Hospital

Abstract

Campylobacter concisus, a Gram-negative bacterium that colonizes the human oral cavity, has been shown to be associated with inflammatory bowel diseases (IBD). The effects of different C. concisus strains on intestinal epithelial expression of Toll like receptors (TLR) have not been investigated. This study examined the effects of C. concisus strains isolated from patients with IBD and controls on expression of TLR4, its co-receptor myeloid differentiation factor (MD)-2; TLR2, TLR5, cyclooxygenase-2 (COX-2) and interleukin (IL)-8 in HT-29 cells.Fourteen oral and enteric C. concisus strains isolated from patients with IBD and healthy controls were co-incubated with HT-29 cells. Expression of TLR4, MD-2, TLR2, TLR5 and COX-2 in HT-29 cells in response to C. concisus infection was examined by Western blot, flow cytometry analysis and immunofluorescent staining visualized by confocal microscope. Production of IL-8 was evaluated by enzyme-linked immunosorbent assay.Both oral and enteric C. concisus strains upregulated expression of TLR4 in HT-29 cells. The levels of glycosylated TLR4 (Gly-TLR4) and surface TLR4 induced by C. concisus strains isolated from patients with IBD were significantly higher than those induced by C. concisus strains isolated from the healthy controls. Four C. concisus strains isolated from patients with IBD induced more than two-fold increase of surface expression of MD-2. C. concisus did not affect expression of TLR2 and TLR5. All C. concisus strains induced production of IL-8 and COX-2 in HT-29 cells.This study shows that some C. concisus strains, most from patients with IBD, upregulate surface expression of TLR4 and MD-2 in HT-29 cells. These data suggest that a potential role of specific C. concisus strains in modulating the intestinal epithelial responses to bacterial LPS needs to be investigated.

Highlights

Campylobacter concisus is a Gram-negative bacterium commonly found in the human oral cavity [1,2]
The concentration of IL-8 induced by the positive control Salmonella enterica serovar Typhimurium LT2 (Salmonella typhimurium) was 9036130 pg/ml. Both oral and enteric C. concisus strains isolated from patients with inflammatory bowel disease (IBD) and controls induced the production of IL-8
This study examined the effects of oral and enteric C. concisus strains isolated from patients with IBD and controls on intestinal epithelial expression of TLR4, myeloid differentiation factor (MD)-2, TLR2, TLR5, COX-2 and IL-8 using an in vitro cell culture model (HT-29 cells)

Summary

Introduction

Campylobacter concisus is a Gram-negative bacterium commonly found in the human oral cavity [1,2]. C. concisus has been shown to be associated with inflammatory bowel disease (IBD) [4,5,6,7,8]. A significantly higher prevalence of C. concisus in intestinal biopsies and fecal samples of patients with IBD was detected as compared with controls [4,5,6,7]. IBD is a chronic inflammatory disorder of the gastrointestinal tract; its most common incidence is in adolescents and young adults [9,10]. The two major types of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). Multiple factors including intestinal microbiota, genetic factors, environmental factors and aberrant responses in the innate and adaptive immune system contribute to the development of IBD [9,10]

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