Clostridium difficile-mediated effects on human intestinal epithelia: Modelling host-pathogen interactions in a vertical diffusion chamber

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Clostridium difficile-mediated effects on human intestinal epithelia : Modelling host-pathogen interactions in a vertical diffusion chamber. / Jafari, Nazila V; Kuehne, Sarah A; Minton, Nigel P; Allan, Elaine; Bajaj-Elliott, Mona.

In: Anaerobe, Vol. 37, 02.2016, p. 96-102.

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Jafari, Nazila V ; Kuehne, Sarah A ; Minton, Nigel P ; Allan, Elaine ; Bajaj-Elliott, Mona. / Clostridium difficile-mediated effects on human intestinal epithelia : Modelling host-pathogen interactions in a vertical diffusion chamber. In: Anaerobe. 2016 ; Vol. 37. pp. 96-102.

Bibtex

@article{e009550a8b7f40498efa1048bcb46b79,
title = "Clostridium difficile-mediated effects on human intestinal epithelia: Modelling host-pathogen interactions in a vertical diffusion chamber",
abstract = "Clostridium difficile infection is one of the leading causes of healthcare associated diarrhoea in the developed world. Although the contribution of C. difficile toxins to disease pathogenesis is now well understood, many facets of host-pathogen interactions between the human intestinal epithelia and the C. difficile bacterium that may contribute to asymptomatic carriage and/or clinical disease remain less clear. Herein, we tested the hypothesis that C. difficile strains mediate intestinal epithelial cell (IEC) antimicrobial immunity via toxin dependent and independent means and that the 'anaerobic' environment has a significant impact on bacterial-IEC interactions. Crosstalk between three C. difficile PCR ribotypes (RT) [RT027 (strain R20291), RT012 (strain 630) and RT017 (strains M68 and CF5)] and IEC cell-lines were investigated. All RTs showed significant engagement with human Toll-like receptors (TLR)-5, TLR2-CD14 and TLR2/6 as measured by IL-8 release from TLR-transfected HEK cells. Co-culture studies indicated minimal impact of R20291 and 630 TcdA and TcdB on bacterial adherence to Caco-2 cells. An apical anaerobic environment had a major effect on C. difficile-T84 crosstalk as significantly greater cytokine immunity and trans-epithelial electrical resistance (TEER) dysfunction was recorded when co-cultures were performed in an Ussing chamber system compared to standard 5% CO2 conditions. Overall, this study suggests that anaerobic C. difficile engagement with human IECs is a complex interplay that involves bacterial and toxin-mediated cellular events.",
keywords = "Bacterial Adhesion, Bacterial Toxins, Caco-2 Cells, Clostridium difficile, Cytokines, Diffusion Chambers, Culture, Enterotoxins, HEK293 Cells, Humans, Immunity, Innate, Intestinal Mucosa, Models, Biological, Journal Article",
author = "Jafari, {Nazila V} and Kuehne, {Sarah A} and Minton, {Nigel P} and Elaine Allan and Mona Bajaj-Elliott",
note = "Copyright {\textcopyright} 2015 Elsevier Ltd. All rights reserved.",
year = "2016",
month = feb,
doi = "10.1016/j.anaerobe.2015.12.007",
language = "English",
volume = "37",
pages = "96--102",
journal = "Anaerobe",
issn = "1075-9964",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Clostridium difficile-mediated effects on human intestinal epithelia

T2 - Modelling host-pathogen interactions in a vertical diffusion chamber

AU - Jafari, Nazila V

AU - Kuehne, Sarah A

AU - Minton, Nigel P

AU - Allan, Elaine

AU - Bajaj-Elliott, Mona

N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2016/2

Y1 - 2016/2

N2 - Clostridium difficile infection is one of the leading causes of healthcare associated diarrhoea in the developed world. Although the contribution of C. difficile toxins to disease pathogenesis is now well understood, many facets of host-pathogen interactions between the human intestinal epithelia and the C. difficile bacterium that may contribute to asymptomatic carriage and/or clinical disease remain less clear. Herein, we tested the hypothesis that C. difficile strains mediate intestinal epithelial cell (IEC) antimicrobial immunity via toxin dependent and independent means and that the 'anaerobic' environment has a significant impact on bacterial-IEC interactions. Crosstalk between three C. difficile PCR ribotypes (RT) [RT027 (strain R20291), RT012 (strain 630) and RT017 (strains M68 and CF5)] and IEC cell-lines were investigated. All RTs showed significant engagement with human Toll-like receptors (TLR)-5, TLR2-CD14 and TLR2/6 as measured by IL-8 release from TLR-transfected HEK cells. Co-culture studies indicated minimal impact of R20291 and 630 TcdA and TcdB on bacterial adherence to Caco-2 cells. An apical anaerobic environment had a major effect on C. difficile-T84 crosstalk as significantly greater cytokine immunity and trans-epithelial electrical resistance (TEER) dysfunction was recorded when co-cultures were performed in an Ussing chamber system compared to standard 5% CO2 conditions. Overall, this study suggests that anaerobic C. difficile engagement with human IECs is a complex interplay that involves bacterial and toxin-mediated cellular events.

AB - Clostridium difficile infection is one of the leading causes of healthcare associated diarrhoea in the developed world. Although the contribution of C. difficile toxins to disease pathogenesis is now well understood, many facets of host-pathogen interactions between the human intestinal epithelia and the C. difficile bacterium that may contribute to asymptomatic carriage and/or clinical disease remain less clear. Herein, we tested the hypothesis that C. difficile strains mediate intestinal epithelial cell (IEC) antimicrobial immunity via toxin dependent and independent means and that the 'anaerobic' environment has a significant impact on bacterial-IEC interactions. Crosstalk between three C. difficile PCR ribotypes (RT) [RT027 (strain R20291), RT012 (strain 630) and RT017 (strains M68 and CF5)] and IEC cell-lines were investigated. All RTs showed significant engagement with human Toll-like receptors (TLR)-5, TLR2-CD14 and TLR2/6 as measured by IL-8 release from TLR-transfected HEK cells. Co-culture studies indicated minimal impact of R20291 and 630 TcdA and TcdB on bacterial adherence to Caco-2 cells. An apical anaerobic environment had a major effect on C. difficile-T84 crosstalk as significantly greater cytokine immunity and trans-epithelial electrical resistance (TEER) dysfunction was recorded when co-cultures were performed in an Ussing chamber system compared to standard 5% CO2 conditions. Overall, this study suggests that anaerobic C. difficile engagement with human IECs is a complex interplay that involves bacterial and toxin-mediated cellular events.

KW - Bacterial Adhesion

KW - Bacterial Toxins

KW - Caco-2 Cells

KW - Clostridium difficile

KW - Cytokines

KW - Diffusion Chambers, Culture

KW - Enterotoxins

KW - HEK293 Cells

KW - Humans

KW - Immunity, Innate

KW - Intestinal Mucosa

KW - Models, Biological

KW - Journal Article

U2 - 10.1016/j.anaerobe.2015.12.007

DO - 10.1016/j.anaerobe.2015.12.007

M3 - Article

C2 - 26708704

VL - 37

SP - 96

EP - 102

JO - Anaerobe

JF - Anaerobe

SN - 1075-9964

ER -