Toll-Like Receptor Function in Acute Wounds

Abstract

Inflammation is an integral part of immune response and supports optimal wound healing in adults. Inflammatory cells such as neutrophils, macrophages, dendritic cells, lymphocytes, and mast cells produce important cytokines, chemokines, and growth factors. These immune cells interact with keratinocytes, fibroblasts, and endothelial cells (ECs), as well as the extracellular matrix within a complicated network that promotes and regulates wound healing. Aberrant and persistent inflammation may result in delayed wound healing, scar formation, or chronic wounds. Targeting the molecules involved in the inflammatory response may have great potential therapeutic value. Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns from microbes or danger-associated molecular patterns from damaged cells. The discovery of TLRs sheds new light on the mechanism by which the inflammatory or innate immune response is initiated in wound healing. Convincing evidence now shows that multiple types of cells, including infiltrating or resident inflammatory cells, keratinocytes, fibroblasts, and ECs, express specific types of TLRs. Experimental reduction of certain TLRs or treatment of wounds with TLR ligands has been shown to affect wound healing. A better understanding of the involvement of TLRs in the innate immune response during skin wound healing may suggest novel strategies to improve the quality of tissue repair. Despite the indisputable role of TLRs in regulating the immune response in acute wound healing, the functions of TLRs that are relevant to human wound healing and chronic wounds are poorly understood.

Immunological Heterogeneity of Healthy Peripheral Blood Stem Cell Donors—Effects of Granulocyte Colony-Stimulating Factor on Inflammatory Responses

“…Taken together these observations suggest that various cells contribute to the IL-6 response during G-CSF therapy. This is similar to the IL-6/CRP responses during infections where both immunocompetent and mesenchymal cells contribute to these responses [ 49 ].…”

“…IL-6 can be released by several immunocompetent as well as mesenchymal cells [ 27 ], and in our present study we included only monocytes together with fibroblasts and normal mesenchymal stem cells. We then used an in vitro model where monocytes and mesenchymal cells were cultured in the presence of TLR agonists; in our opinion this is a more physiological model than culture in medium alone because a wide range of endogenous TLR ligands have now been identified and are expected to be present in the in vivo microenvironments of these cells [ 49 ]. A strong/significant alteration of the IL-6 release in the presence of G-CSF was defined as a two-fold alteration.…”

Enhanced Wound Healing- and Inflammasome-Associated Gene Expression in TNFAIP3-Interacting Protein 1- (TNIP1-) Deficient HaCaT Keratinocytes Parallels Reduced Reepithelialization

“…Mediators of Inflammation pro-IL-1β, and pro- showing that expression of these components is not absolutely dependent on de novo priming by TLR agonists. Despite a general view of TLR3 agonism by poly (I:C) being favorable to wound healing [72], as shown in this report, TNIP1 deficiency appears to have established a state of overreaction to any incoming TLR-mediated signal leading to previously unrecognized negative consequences from excessive or imbalanced responses. While the induction of ASC expression in TNIP1-deficient HaCaT cells could lead to this end, the potential role of products from other induced genes, e.g., NLRP10, should also be considered.…”

Wound healing: cellular mechanisms and pathological outcomes

“…T cells and macrophages, by binding pattern recognition receptors to elicit downstream inflammatory pathways [16]. A subsequent release of pro-inflammatory cytokines and chemokines attracts circulating leucocytes to the site of injury (reviewed in [17]).…”