Resistance versus susceptibility to Leishmania: genetic differences in a population of English Setter dogs

Leishmaniosis is a parasitic disease caused by kinetoplastid protozoa belonging to the genus Leishmania, which is transmitted to vertebrates via infected female phlebotomine sand flies. The main causative agent of canine leishmaniasis in Europe is L. infantum, which is highly diffused in the Mediterranean area and causes a spectrum of clinical signs that varies greatly from asymptomatic/mild to a very severe disease in dogs. The natural susceptibility or resistance to Leishmania infection is the result of complex interactions between the parasite and the host immune system. These interactions are due to the differences among individuals, and their genetic asset. Various genetic mutations in different breeds have been suggested as potential genetic markers to be used in the study of L. infantum infection resistance/susceptibility. Aim of this study was to evaluate the genotype of 4 SNPs (CBD1 gene), described as associated with resistance (rs852670798 and rs853079810) or susceptibility (rs850814192 and rs851268228) to L. infantum infection, in a cohort of 12 English Setter dogs, raised sharing the same habitat (private hunting dogs kept in outdoor kennel) and same repellent treatment for leishmaniasis vector (phlebotomine sand flies), but with different responses to this infection. The dogs in this study were 10 males and 2 females, age ranging between 1 to 13 years (mean age ~6 years). Four age classes (with three dog each) were defined and identified as I to IV: age ≤2 years old, 2 < age ≤4 years old, 4 < age <8 years old, and age ≥8 years old. Of these dogs, sampled during spring 2021, 8 animals were positive to the ELISA test for L. infantum infection, while 4 animals were negative. A preliminary analysis of the obtained data showed no correlation between the different haplotypes found in the cohort and the ELISA test result (p-value =0.49). Nevertheless, as suspected, a quadratic association between the age of the animal and the ELISA test result was found (R2 of the model =35.2%, p-value =0.05). A follow-up on the cohort will be performed and the animals will be re-evaluated in the following infectious seasons to separate the effect of the age from the genetic one. Furthermore, the samples were genotyped using a high density SNP chip and we are testing different SNP-based approaches to investigate other possible genetic effects on resistance/susceptibility of L. infantum infection.