Abstract
The outcome of infection with Leishmania infantum in dogs is variable, which is thought to be due to the nature of the immune response mounted by the host. As a consequence, the clinical signs and severity of canine leishmaniosis vary between individual dogs. Host immunogenetic factors might play an important role in determining the outcome of infection. The aim of this study was to examine polymorphisms in innate and adaptive immune response genes, to determine whether any of these were associated with susceptibility or resistance to L. infantum infection. Genomic DNA was obtained from two groups: pet dogs in endemic regions of Europe and a group of Beagles exposed to sand fly infection as part of a vaccine study. Genotyping was performed using a SNP (single nucleotide polymorphism) array for selected immune response genes. The first part of the study compared 62 clinical cases with 101 clinically unaffected dogs that were seronegative for Leishmania antibodies. One SNP in the CIITA gene demonstrated a significantly higher minor allele frequency in the case group, compared with the control group at the individual SNP level after permutation, but was not significant after correction for multiple testing. The second part of the study examined 48 Beagle dogs exposed to L. infantum over two transmission seasons. Twenty-seven dogs with a resistant phenotype (no evidence of clinical disease, seronegative at the end of the study period, negative on lymph node culture and only transiently PCR positive in bone marrow) were compared with 21 dogs demonstrating a susceptible phenotype (clinical disease, seropositive, positive lymph node culture and consistently PCR positive in bone marrow). Three SNPs in TLR3, two SNPs in PTPN22 and one SNP in TLR4 and IL1A were associated with the susceptible phenotype in the Beagle group at the individual SNP level after permutation analysis, but were not significant after correction for multiple testing. Further validation of these SNPs is required in a larger cohort of dogs, ideally with extreme phenotypes to confirm an association with the outcome of L. infantum infection.
Highlights
Canine leishmaniosis is caused by the protozoan parasite Leishmania infantum, which is responsible for zoonotic visceral and cutaneous leishmaniosis in humans (Gramiccia and Gradoni, 2005)
Definitive diagnosis of canine leishmaniosis can be difficult to achieve, there is a high index of suspicion for individuals with clinical signs of overt leishmaniosis and a highly positive serology result (Paltrinieri et al, 2010)
The aim of this study was to interrogate polymorphisms in candidate innate and adaptive immune response genes in dogs naturally infected with L. infantum to determine whether there are associations with clinical disease and/or infection status
Summary
Canine leishmaniosis is caused by the protozoan parasite Leishmania infantum, which is responsible for zoonotic visceral and cutaneous leishmaniosis in humans (Gramiccia and Gradoni, 2005). Diagnosis of canine leishmaniosis is based on the presence of clinical signs and clinicopathological abnormalities compatible with disease, alongside diagnostic methods of determining infection with L. infantum (Solano-Gallego et al, 2009). A definitive diagnosis of canine leishmaniosis can be difficult to achieve, there is a high index of suspicion for individuals with clinical signs of overt leishmaniosis and a highly positive serology result (Paltrinieri et al, 2010). When dogs tests, including the indirect present with a low clinical suspicion index, or where anti- Leishmania antibody reactivity is low, multiple diagnostic tests might be required to confirm the diagnosis (Solano-Gallego et al, 2009; Paltrinieri et al, 2010)
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