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.

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., McBain, A. J., Cruickshank, S. M., & 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
• 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
• Contract Date: May 14, 2018