The innate immune system, toll-like receptors and dermal wound healing: A review.

Wound healing is a complex physiological process comprised of discrete but inter-related and overlapping stages, requiring exact timing and regulation to successfully progress, yet occurs spontaneously in response to injury. It is characterised by four phases, coagulation, inflammation, proliferation and remodelling. Each phase is predominated by particular cell types, cytokines and chemokines. The innate immune system represents the first line of defence against invading microorganisms. It is entirely encoded with the genome, and comprised of a cellular response with specificity provided by pattern recognition receptors (PRRs) such as toll-like receptors (TLRs). TLRs are activated by exogenous microbial pathogen associated molecular patterns (PAMPs), initiating an immune response through the production of pro-inflammatory cytokines and further specialist immune cell recruitment. TLRs are also activated by endogenous molecular patterns termed damage associated molecular patterns (DAMPs). These ligands, usually shielded from the immune system, act as alarm signals alerting the immune system to damage and facilitate the normal wound healing process. TLRs are expressed by cells essential to wound healing such as keratinocytes and fibroblasts, however the specific role of TLRs in this process remains controversial. This article reviews the current knowledge on the potential role of TLRs in dermal wound healing where inflammation arising from pathogenic activation of these receptors appears to play a role in chronic ulceration associated with diabetes, scar hypertrophy and skin fibrosis. Crown