Monocytes Display Altered Inflammatory Profiles in Individuals with Diabetic Foot Ulcers Indicating Monocyte Dysfunction

ABSTRACT

Diabetic foot ulcers (DFUs) often exhibit impaired healing. Macrophage imbalance driven by persistent inflammation is one contributing factor, with a predominance of inflammatory over anti‐inflammatory macrophages in non‐healing ulcers. Monocytes, precursors of macrophages, are skewed towards an inflammatory phenotype in diabetes. Here, we investigated whether monocyte inflammatory skewing is further exacerbated in individuals with DFUs and explored how it relates to an individual's metabolic (HbA1c and lipids) profile. Monocyte inflammatory profile was assessed by examining phenotypic markers, gene expression, and cytokine production. We observed an elevation in total monocytes and the intermediate subset in the DFU group compared with healthy individuals. In addition, an impaired monocyte profile was seen in the DFU group, with a suppression of both inflammatory (CD86, TLR2, and TLR4) and anti‐inflammatory (CD163) markers, accompanied by the downregulation of distinct inflammatory and anti‐inflammatory genes. Despite a suppressed phenotype, DFU monocytes showed an increased basal TNF and IFN‐γ production, indicating low‐grade inflammation. Further, in exploratory analysis, monocyte CD86 and CD163 inversely correlated with HbA1c, while CD163 negatively correlated with cholesterol/HDL‐C and triglycerides, suggesting links between metabolic control and monocyte phenotype. Taken together, the impaired monocyte profile indicates underlying pathogenic inflammation and monocyte dysfunction in people with DFUs, suggesting the monocyte profile could serve as a potential biomarker for immunomodulation in DFU.