Immune Mediator Profile in the Inflammatory Microenvironment Reveals Potential Biomarkers of Wound Healing in Localized Cutaneous Leishmaniasis

Localized cutaneous leishmaniasis (LCL) is the most prevalent form of leishmaniasis, with infection control primarily dependent on cell-mediated immunity. Lesion healing results from a complex interplay among immune cells and soluble mediators. Using Luminex technology, we evaluated circulating and lesion microenvironment immune mediators, including chemokines, cytokines, and growth factors, in patients with LCL and nonspecific dermatitis. A robust proinflammatory response was observed in the lesion microenvironment of LCL patients, characterized by elevated levels of growth factors, important immune mediators potentially involved in tissue repair. Predictive modeling identified FGF, G-CSF, GM-CSF, IL-2, and IL-9 as key immune mediators distinguishing LCL from nonspecific dermatitis. Our results reveal that LCL presents a distinct soluble immune mediator signature from nonspecific dermatitis, exhibiting a set of biomarkers that not only define its immune mediator signature but also signal a possible role in the tissue repair process. Furthermore, we characterized the profile of soluble immune mediators of LCL patients, categorized according to the time evolution lesion. Our analysis revealed a predominance of biomarkers within the lesion microenvironment in patients with recent lesions (< 2 months of evolution). On the other hand, in late lesions patients (> 2 months of evolution), our data showed a predominance of biomarkers in the systemic circulation. Collectively, these findings provide novel insights into the immunopathogenesis of LCL and highlight candidate immune mediators for targeted prognostic evaluation.