A novel 3D skin explant model to study anaerobic bacterial infection

Maboni, G., Davenport, R., Sessford, K., Baiker, K., Jensen, T.K., Blanchard, A.M. ORCID: 0000-0001-6991-7210, Wattegedera, S., Entrican, G. and Tötemeyer, S., 2017. A novel 3D skin explant model to study anaerobic bacterial infection. Frontiers in Cellular and Infection Microbiology, 7: 404. ISSN 2235-2988

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Abstract

Skin infection studies are often limited by financial and ethical constraints, and alternatives, such as monolayer cell culture, do not reflect many cellular processes limiting their application. For a more functional replacement, 3D skin culture models offer many advantages such as the maintenance of the tissue structure and the cell types present in the host environment. A 3D skin culture model can be set up using tissues acquired from surgical procedures or post slaughter, making it a cost effective and attractive alternative to animal experimentation. The majority of 3D culture models have been established for aerobic pathogens, but currently there are no models for anaerobic skin infections. Footrot is an anaerobic bacterial infection which affects the ovine interdigital skin causing a substantial animal welfare and financial impact worldwide. Dichelobacter nodosus is a Gram-negative anaerobic bacterium and the causative agent of footrot. The mechanism of infection and host immune response to D. nodosus is poorly understood. Here we present a novel 3D skin ex vivo model to study anaerobic bacterial infections using ovine skin explants infected with D. nodosus. Our results demonstrate that D. nodosus can invade the skin explant, and that altered expression of key inflammatory markers could be quantified in the culture media. The viability of explants was assessed by tissue integrity (histopathological features) and cell death (DNA fragmentation) over 76 h showing the model was stable for 28 h. D. nodosus was quantified in all infected skin explants by qPCR and the bacterium was visualized invading the epidermis by Fluorescent in situ Hybridization. Measurement of pro-inflammatory cytokines/chemokines in the culture media revealed that the explants released IL1β in response to bacteria. In contrast, levels of CXCL8 production were no different to mock-infected explants. The 3D skin model realistically simulates the interdigital skin and has demonstrated that D. nodosus invades the skin and triggered an early cellular inflammatory response to this bacterium. This novel model is the first of its kind for investigating an anaerobic bacterial infection.

Item Type: Journal article
Publication Title: Frontiers in Cellular and Infection Microbiology
Creators: Maboni, G., Davenport, R., Sessford, K., Baiker, K., Jensen, T.K., Blanchard, A.M., Wattegedera, S., Entrican, G. and Tötemeyer, S.
Publisher: Frontiers Research Foundation
Date: 2017
Volume: 7
ISSN: 2235-2988
Identifiers:
NumberType
10.3389/fcimb.2017.00404DOI
Rights: Copyright © 2017 Maboni, Davenport, Sessford, Baiker, Jensen, Blanchard, Wattegedera, Entrican and Tötemeyer. 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.
Divisions: Schools > School of Animal, Rural and Environmental Sciences
Depositing User: Linda Sullivan
Date Added: 16 Aug 2018 11:21
Last Modified: 16 Aug 2018 11:21
URI: http://irep.ntu.ac.uk/id/eprint/34343

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