Breed-specific immune tolerance to Leishmania infantum in a native Mediterranean canine population

Canine leishmaniosis caused by Leishmania infantum remains a major zoonotic concern in the Mediterranean basin, where native breeds may have evolved adaptive immune mechanisms against infection. This study evaluated cytokine and growth factor profiles in Fonni dogs, a Sardinian native breed, and German Shepherds exposed to L. infantum and other vector-borne pathogens. Samples were collected as part of routine clinical practice, and no procedures were performed for research purposes. Fifty-nine clinically healthy dogs were analyzed for seropositivity to Anaplasma phagocytophilum , Ehrlichia canis , Leptospira spp., Leishmania infantum , and Rickettsia spp., and for serum levels of eleven cytokines and growth factors using a multiplex immunoassay. Fonni dogs showed significantly higher serum levels of IL-10, NGF-β, IFN-γ, TNF-α, and VEGF-α compared with German Shepherds. L. infantum and Rickettsia spp. positive animals exhibited elevated IL-10, NGF-β, and TNF-α concentrations. Age influenced several cytokines, with young Fonni dogs displaying the highest IL-10 and NGF-β values, while TNF-α and MCP-1 increased with age. Correlation and principal component analyses revealed distinct clustering between breeds, highlighting coordinated regulation of pro-inflammatory and angiogenic mediators (IL-6, TNF-α, MCP-1, VEGF-α). The elevated values of several cytokines in Fonni dogs suggest a breed-specific immune tolerance-like phenotype consistent with reduced immunopathology under endemic exposure. These data support a breed-associated regulatory/pro-inflammatory immune balance in Fonni dogs, consistent with a tolerance-like immune phenotype under endemic exposure.