Evaluation of the Cutaneous Immunological Milieu Before and After Treatment With Meglumine Antimoniate in Dogs Naturally Affected by Leishmaniosis due to Leishmania infantum.

Abstract

BACKGROUND: Canine leishmaniosis (CanL) is a zoonotic disease of variable severity. The typical immune response is driven by an exaggerated humoral immune response. Protective immunity is mediated by pro-inflammatory cytokines that enhance macrophage leishmanicidal activity. OBJECTIVE: To evaluate the cutaneous and the systemic immune responses as well as the cutaneous parasitic load in affected dogs before and after 28 days of treatment with meglumine antimoniate. ANIMALS: Twelve dogs with CanL and skin lesions, treated with meglumine antimoniate at a target dose of 100 mg/kg subcutaneously every 24 h, were prospectively enrolled. METHODS AND MATERIALS: Before and after 28 days of treatments, blood samples and skin biopsies were collected. Circulating levels of host defence peptides, leptin and cytokines were determined via enzyme-linked immunosorbent assay (ELISA). Paraffin-embedded skin biopsies were processed for routine immunofluorescence and positive cells were identified using commercially available anti-canine antibodies. Parasitic load also was determined via molecular methods. All variables were statistically analysed with the significance level set at 0.05. RESULTS: Among the cutaneous cell types investigated, there was a decrease in the number of T-box transcription factor TBX21 (Tbet) (p = 0.016), GATA binding protein 3 (GATA3) (p = 0.016), interleukin (IL)-17A(p = 0.03) cells and neutrophils (p = 0.008) after treatment, whereas there were no significant changes in forkhead box protein P3 (FoxP3) regulatory T and ionised calcium-binding adaptor molecule 1 (Iba1) cells. A lack of change in serum concentration of inflammatory mediators was found. Finally, cutaneous parasitic load was significantly lower after treatment (p = 0.03). CONCLUSIONS AND CLINICAL RELEVANCE: The results of this study show that the reduction of cutaneous parasitic load after meglumine antimoniate treatment results in downregulation of innate and adaptive cutaneous inflammatory responses.