Breed-specific variation in canine cytokine profiles in a leishmaniosis-endemic region

Leishmania infantum is a zoonotic intracellular parasite endemic to Mediterranean countries and infects various hosts, including dogs, which are its primary reservoir. Canine immune response to L. infantum varies by breed and is mediated through a balance between Th1- and Th2-associated cytokines. This study aimed to compare serum cytokine profiles in non-infected dogs of three purebred breeds-Cirneco dell'Etna, Pharaoh Hound, and Boxer-and crossbred dogs, living in endemic Mediterranean regions. A total of 42 clinically healthy, non-infected dogs were screened through serological (IFI, ELISA) and molecular (qPCR) methods to confirm the absence of L. infantum infection. Serum levels of IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, and IL-12 were quantified by ELISA, and statistical analyses including mixed models, correlation matrices, and multivariate sparse Partial Least Squares Regression (sMBPLSR) were applied. No significant differences in cytokine profiles were found based on sex or age. However, clear inter-breed differences were detected. Cirneco dell'Etna and Pharaoh hound showed similar cytokine patterns, with lower IL-6 and IL-8 levels than Boxer and crossbred dogs. IL-2 was significantly higher in crossbreds. Strong correlations between IFN-γ and IL-8 were absent in Boxers but present in other breeds. Cirneco dell'Etna dogs exhibited negative regressions between IL-2 and Th2 cytokines, suggesting a Th1-biased profile. These findings support that Cirneco dell'Etna and Pharaoh hound, closely related genetically to the Leishmania-resistant Ibizan hound, may possess inherent immunological traits favouring resistance via a controlled Th1 response. This suggests potential breed-dependent immunogenetic mechanisms underlying differential susceptibility to L. infantum infection.