Leishmania braziliensis infection enhances adipokine and cytokine production and severity of cutaneous leishmaniasis in patients with obesity

Cutaneous leishmaniasis (CL) is more severe in obese than in lean individuals. Here we investigated the contribution of adipose tissue to the severity of CL in 39 obese and 43 lean CL patients, along with 8 healthy subjects (HS). Skin and subcutaneous biopsies were evaluated by histopathology and cytokine/adipokine analysis. Obese patients showed a lower response rate to antimony therapy (41% vs. 70.4%) and longer healing times (P < 0.05). Histopathological analysis revealed denser dermal and subcutaneous inflammatory infiltrates in obese patients, predominantly composed of macrophages and lymphocytes, associated with high adipose tissue production of CCL-2. Obese patients exhibited increased dermal expression of TNF, IL-1β, IL-17, and granzyme B, all markers associated with disease severity. Leptin levels correlated positively with these inflammatory mediators, and leptin neutralization reduced their production. Leishmania infection also altered adipokine profiles: adiponectin levels were 10.5-fold higher in lean CL than in lean HS, while leptin levels were 3.1-fold higher in obese CL than in obese HS (P < 0.05). These findings indicate that in L. braziliensis infection, adipocyte and dermal cells drive inflammatory cell infiltration into both subcutaneous and dermal compartments, accompanied by marked adipokine and cytokine production that amplifies tissue pathology.