Role of Innate Immune Cells in Chronic Diabetic Wounds

Diabetic foot ulcers are one of the common secondary complications associated with diabetes and are characterized by delayed or absence of healing. Of the several factors contributing to poor healing, chronic low-grade inflammation significantly worsens wound healing resulting in adverse outcomes. As the innate immune system plays a vital role in wound healing, a closer look at their alterations may provide insights into developing novel treatment strategies to promote healing. In this review, we discuss the role of the innate immune system in driving chronic inflammation both at the wound site and at the systemic level, resulting in poor healing outcomes. Specifically, we highlight the findings from preclinical and clinical studies that describe the dysregulations of the innate system at the cellular and molecular level and how they contribute to low-grade chronic inflammation in wounds. Our review of the literature shows that preexisting low-grade inflammation, which is associated with altered myeloid cell phenotype and function, is key to impaired wound healing responses in individuals with diabetes. Hence, we suggest that modulating circulating myeloid cell function and low-grade chronic inflammation could be a helpful strategy in promoting diabetic foot ulcer healing.