Breed-specific immune regulation under endemic exposure to Leishmania infantum and other vector-borne pathogens in a native Mediterranean canine population.

Abstract

BACKGROUND: Canine leishmaniosis caused by Leishmania infantum remains a major zoonotic concern in the Mediterranean basin, where native breeds may have evolved adaptive immune mechanisms under long-term endemic exposure. The Fonni dog, indigenous to Sardinia, may represent a model of such adaptation. This study aimed to compare cytokine and growth factor profiles between Fonni dogs and German Shepherd dogs exposed to L. infantum and other vector-borne pathogens, to investigate potential breed-associated immune regulatory patterns. METHODS: Fifty-nine clinically healthy dogs (Fonni and German Shepherds) living in endemic areas were included. Serum samples were tested for antibodies against Anaplasma phagocytophilum, Ehrlichia canis, Leptospira spp., Leishmania infantum, and Rickettsia spp. Concentrations of eleven cytokines and growth factors were measured using a multiplex bead-based immunoassay. Statistical analyses evaluated differences between breeds, associations with serological status and age, as well as correlation matrices and principal component analysis to explore clustering patterns among immune mediators. RESULTS: Fonni dogs showed significantly higher serum concentrations of IL-10, NGF-β, IFN-γ, TNF-α, and VEGF-α compared with German Shepherds. Seropositive dogs for L. infantum and Rickettsia spp. exhibited increased levels of IL-10, NGF-β, and TNF-α. Age influenced cytokine expression, with young Fonni dogs displaying the highest IL-10 and NGF-β values, whereas TNF-α and MCP-1 concentrations increased with age. Correlation and principal component analyses revealed distinct breed-specific clustering, highlighting coordinated regulation of pro-inflammatory and angiogenic mediators, particularly IL-6, TNF-α, MCP-1, and VEGF-α. CONCLUSIONS: The elevated levels of several cytokines and growth factors in Fonni dogs suggest a breed-associated immune phenotype characterized by a regulatory/pro-inflammatory balance consistent with a tolerance-like response under endemic exposure. These findings support the hypothesis that native breeds such as the Fonni dog may have developed adaptive immunological mechanisms that limit immunopathology while maintaining effective responses in areas endemic for canine vector-borne pathogens.