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Microbial host interactions and impaired wound healing in mice and humans: defining a role for BD14 and NOD2

Williams, Helen; Campbell, Laura; Crompton, Rachel A.; Singh, Gurdeep; McHugh, Brian J.; Davidson, Donald J.; McBain, Andrew J.; Cruickshank, Sheena M.; Hardman, Matthew J.

Authors

Helen Williams

Laura Campbell

Rachel A. Crompton

Gurdeep Singh

Brian J. McHugh

Donald J. Davidson

Andrew J. McBain

Sheena M. Cruickshank



Abstract

Chronic wounds cause significant patient morbidity and mortality. A key factor in their etiology is microbial infection, yet skin host-microbiota interactions during wound repair remain poorly understood. Microbiome profiles of non-infected human chronic wounds are associated with subsequent healing outcome. Furthermore, poor clinical healing outcome was associated with increased local expression of the pattern recognition receptor NOD2. To investigate NOD2 function in the context of cutaneous healing, we treated mice with the NOD2 ligand muramyl dipeptide (MDP) and analyzed wound repair parameters and expression of anti-microbial peptides. MDP treatment of littermate controls significantly delayed wound repair associated with reduced re-epithelialization, heightened inflammation and upregulation of murine β-Defensins (mBD) 1, 3 and particularly 14. We postulated that although BD14 might impact on local skin microbial communities it may further impact other healing parameters. Indeed, exogenously administered mBD14 directly delayed mouse primary keratinocyte scratch wound closure in vitro. To further explore the role of mBD14 in wound repair, we employed Defb14-/- mice, and showed they had a global delay in healing in vivo, associated with alterations in wound microbiota. Taken together these studies suggest a key role for NOD2-mediated regulation of local skin microbiota which in turn impacts on chronic wound etiology.

Citation

Williams, H., Campbell, L., Crompton, R. A., Singh, G., McHugh, B. J., Davidson, D. J., …Hardman, M. J. (2018). Microbial host interactions and impaired wound healing in mice and humans: defining a role for BD14 and NOD2. Journal of Investigative Dermatology, 138(10), 2264-2274. https://doi.org/10.1016/j.jid.2018.04.014

Journal Article Type Article
Acceptance Date Apr 9, 2018
Online Publication Date Apr 30, 2018
Publication Date Oct 1, 2018
Deposit Date May 12, 2018
Publicly Available Date May 1, 2019
Journal Journal of Investigative Dermatology
Print ISSN 0022-202x
Electronic ISSN 1523-1747
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 138
Issue 10
Pages 2264-2274
DOI https://doi.org/10.1016/j.jid.2018.04.014
Keywords Cell Biology; Biochemistry; Molecular Biology; Dermatology
Public URL https://hull-repository.worktribe.com/output/827409
Publisher URL https://www.sciencedirect.com/science/article/pii/S0022202X18318931
Copyright Statement © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

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