Immune and Genomic Analysis of Boxer Dog Breed and Its Relationship with Leishmania infantum Infection

SIMPLE SUMMARY: Leishmaniosis is a zoonotic disease, endemic in 88 countries, including those from the Mediterranean region. Several authors indicate differences in susceptibility and resistance to leishmaniosis in different canine breeds, with boxer being one of the breeds with a higher prevalence of the disease. This study analyzes the serum profiles of cytokines related to the immune response, together with the screening of genomic variants fixed in boxer breed samples, to understand their differential susceptibility to L. infantum infection. The results of this study indicate new pathways related to L. infantum infection and immune response in boxers, involving genes related to interleukin and toll-like receptors, as well as to the immune system and the regulation of expression. Future studies are required to elucidate the role of specific genes in the L. infantum infection mechanism in this canine breed. ABSTRACT: Leishmaniosis, one of the most important zoonoses in Europe, is caused by Leishmania infantum, an intracellular protozoan parasite. This disease is endemic in the Mediterranean area, where the main reservoir is the dog. Several studies indicate a possible susceptibility to L. infantum infection with clinical signs in some canine breeds. One of them is the boxer breed, which shows a high prevalence of disease. In this study, immunological and genomic characterization of serum samples from boxer dogs living in the Mediterranean area were evaluated to analyze the immune response and the possible genetic explanation for this susceptibility. Serum levels of cytokines IFN-γ, IL-2, IL-6, IL-8, and IL-18 were determined by ELISA commercial tests, while the genotyping study was performed using the CanineHD DNA Analysis BeadChip. The results show relevant differences in the serum levels of cytokines compared to published data on other canine breeds, as well as sequence changes that could explain the high susceptibility of the boxer breed to the disease. Concretely, polymorphic variants in the CIITA, HSF2BP, LTBP1, MITF, NOXA1, PKIB, RAB38, RASEF, TLE1, and TLR4 genes were found, which could explain the susceptibility of this breed to L. infantum infection.