School of Medicine

Chronic wounds are a major source of morbidity in the United States, affecting an estimated 5.7 million people per year at a cost of 20 billion dollars annually. Underlying factors, such as diabetes, poor perfusion due to vascular disease, or infection, complicates many of these wounds. The normal wound healing process proceeds through three stages, which are precisely choreographed. Appropriate early inflammation is required to sterilize and debride the wound, followed by an orderly transition to repair processes. Inappropriate inflammation can result in pathologic wound healing. It is well recognized that the commensal organisms present in the gut play an important role in mediating gastrointestinal immunity and inflammatory responses through their interaction with innate pathogen recognition receptors, such as TLRs. The skin is also continuously exposed to potential pathogens and possesses unique microflora. Recently, the common cutaneous commensal, Staphylococcus epidermidis, was shown to help establish an inflammatory homeostasis by reducing inflammation in the skin under normal conditions. This is accomplished through activation of TLR-2 by the bacteria's unique lipotechoic acid, which leads to suppression of a NF-kB mediated inflammatory pathway activated by TLR3. Recent research has also shown that TLR3 recognizes cutaneous injury in addition to its traditional dsRNA ligand, and is important for inducing inflammation and in wound healing. Inflammation is essential early in the wound healing process, but detrimental later on. Therefore, the timing and degree of inflammation must be tightly regulated. In light of these interactions, and the presence of much greater amounts of commensal bacteria in chronic wounds, I evaluated the role of TLRs and S. epidermidis LTA in modulating the wound healing process. TLR3 KO mice demonstrated altered gene expression following wounding, but unlike other reports, we observed delayed healing only on days 2-4. Exposure to LTA significantly delayed the wound healing respons.