Immunomodulatory Properties of Host Defence Peptides in Skin Wound Healing

Abstract

Cutaneous wound healing is a vital biological process that aids skin regeneration upon injury. Wound healing failure results from persistent inflammatory conditions observed in diabetes, or autoimmune diseases like psoriasis. Chronic wounds are incurable due to factors like poor oxygenation, aberrant function of peripheral sensory nervature, inadequate nutrients and blood tissue supply. The most significant hallmark of chronic wounds is heavily aberrant immune skin function. The immune response in humans relies on a large network of signalling molecules and their interactions. Research studies have reported on the dual role of host defence peptides (HDPs), which are also often called antimicrobial peptides (AMPs). Their duality reflects their potential for acting as antibacterial peptides, and as immunodulators that assist in modulating several biological signalling pathways related to processes such as wound healing, autoimmune disease, and others. HDPs may differentially control gene regulation and alter the behaviour of epithelial and immune cells, resulting in modulation of immune responses. In this review, we shed light on the understanding and most recent advances related to molecular mechanisms and immune modulatory features of host defence peptides in human skin wound healing. Understanding their functional role in skin immunity may further inspire topical treatments for chronic wounds.

Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds

“…It is unclear exactly what control of wound inflammation might look like. It could be by the use of biomaterial dressings that might modulate the immune system or through the modulation of the skin's own host defence peptides to clear an infection and alter the inflammatory phase [65][66][67][68][69]. It might be as simple as reducing the number of monocytes/macrophages entering the wound by repurposing of drugs, for example the use of anti-integrin antibodies to reduce the macrophage load [70].…”

Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers

“…Wound healing comprises a complex and dynamic series of cellular and biochemical events which consists of the following four overlapping phases: hemostasis, inflammation, proliferation, and remodeling [ 5 , 27 , 28 , 29 ]. The hemostasis phase begins with constriction of the injured blood vessels and activation of platelets to form a fibrin clot to stop the bleeding [ 27 , 30 ]. Subsequently, the inflammatory phase initiates with the recruitment of neutrophils to the clot as a first line of defense against pathogens to remove debris, in order to provide a propitious environment for wound healing [ 27 , 28 , 30 ].…”

“…The hemostasis phase begins with constriction of the injured blood vessels and activation of platelets to form a fibrin clot to stop the bleeding [ 27 , 30 ]. Subsequently, the inflammatory phase initiates with the recruitment of neutrophils to the clot as a first line of defense against pathogens to remove debris, in order to provide a propitious environment for wound healing [ 27 , 28 , 30 ]. Neutrophils reach their peak population between 24 and 48 h after injury, after which they reduce greatly in number, and macrophages, in turn, arrive at the wound site and continue clearing debris [ 27 , 28 ].…”

“…Macrophages secrete growth factors and proteins that attract adaptive immune system cells to the wound site, such as Langerhans cells, dermal dendritic cells and T cells, which are involved either in the clearance of cellular debris or in the combat of infection [ 27 , 28 ]. Once the wound has been cleaned out and the inflammation decrease, the proliferative phase occurs with the following three different stages: filling of the wound with granulation tissue, contraction of the wound margins, and covering of the wound with epithelial cells, also called re-epithelization [ 27 , 28 , 30 ]. Finally, the remodeling phase takes place with collagen fiber reorganization, tissue remodeling and maturation, and an overall increase in the tensile strength can be observed [ 27 , 28 , 30 ].…”

“…Once the wound has been cleaned out and the inflammation decrease, the proliferative phase occurs with the following three different stages: filling of the wound with granulation tissue, contraction of the wound margins, and covering of the wound with epithelial cells, also called re-epithelization [ 27 , 28 , 30 ]. Finally, the remodeling phase takes place with collagen fiber reorganization, tissue remodeling and maturation, and an overall increase in the tensile strength can be observed [ 27 , 28 , 30 ].…”