TY - JOUR
T1 - Microbial host interactions and impaired wound healing in mice and humans: defining a role for BD14 and NOD2
AU - Williams, Helen
AU - Campbell, Laura
AU - Crompton, Rachel Anne
AU - Singh, Gurdeep
AU - McHugh, Brian J.
AU - Davidson, Donald D
AU - Mcbain, Andrew
AU - Cruickshank, Sheena
AU - Hardman, Matthew J
PY - 2018
Y1 - 2018
N2 - 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. We investigated microbiome profiles of non-infected human chronic wounds and showed that reduced diversity was 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.
AB - 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. We investigated microbiome profiles of non-infected human chronic wounds and showed that reduced diversity was 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.
U2 - 10.1016/j.jid.2018.04.014
DO - 10.1016/j.jid.2018.04.014
M3 - Article
SN - 0022-202X
JO - The Journal of Investigative Dermatology
JF - The Journal of Investigative Dermatology
ER -