Humoral Responses and Ex Vivo IFN-γ Production after Canine Whole Blood Stimulation with Leishmania infantum Antigen or KMP11 Recombinant Protein

Abstract

The effect of Leishmania infantum soluble antigen (LSA) and recombinant Kinetoplastid Membrane Protein 11 (rKMP11) on the induction of ex vivo specific IFN-γ (n = 69) and antibody responses (n = 108) was determined in dogs. All dogs were tested for serological response to both antigens and divided into Group 1: healthy (Asturias, Spain, n = 26), Group 2: sick (n = 46), Group 3: healthy Ibizan hounds (Mallorca, Spain, n = 22) and Group 4: healthy (Bari, Italy, n = 14). Antibody levels were higher for LSA when compared to rKMP11 (p = 0.001). Ibizan hounds were all seronegative to rKMP11 and 18% were low seropositive to LSA. Sick dogs presented higher antibody response to both antigens compared to the rest of the groups (p < 0.0001). All groups showed higher IFN-γ levels after LSA compared to rKMP11 responses (p < 0.05). The highest response to LSA was found in Ibizan hounds (p < 0.05). IFN-γ to LSA and rKMP11 stimulation was observed in 34% and in 2.8% of the sick dogs, respectively. Here, we demonstrated that anti-rKMP11 antibodies are mainly present in dogs with moderate to severe disease. Furthermore, cellular immune response measured by specific ex vivo IFN-γ production was more intense to LSA than stimulated to rKMP11.

Immunological and genomic characterization of Ibizan Hound dogs in an endemic Leishmania infantum region

“…Aslan et al [ 34 ] found that IL-2 expression was negatively correlated with splenic parasite loads in experimentally infected dogs [ 31 ]. Our results are in agreement with previous data, indicating a natural resistance against leishmaniosis in Ibizan Hounds compared to other canine breeds [ 11 , 24 , 32 ]. The gene encoding for IL-2 is located at chromosome 19 and presents four exons.…”

“…Moreover, the upregulation of IFN-γ has been correlated with low disease severity [ 23 ]. Furthermore, stimulation with Leishmania infantum soluble antigen (LSA) in Ibizan Hound dogs provokes higher IFN-γ serum levels than in other healthy or sick dog breed [ 24 ]. The IFNG gene is located at chromosome 10 and presents four exons that codify a unique protein with 166 amino acids.…”

Immune and genomic characterization of Ibizan hound and its relationship with Leishmania infantum infection

“…Aslan et al (2016) found that IL-2 expression was negatively correlated with splenic parasite loads in experimentally infected dogs [37]. Our results are in agree with several authors, which suggest a natural resistance in Ibizan hound against leishmaniosis compared to other canine breeds [23,38,39]. The gene encodes for IL-2 is located at chromosome 19 and presents four exons.…”

“…Previously, this upregulation of IFN-γ has been correlated with low severity of disease [28]. Furthermore, stimulation with Leishmania infantum soluble antigen (LSA) in Ibizan hound dogs provokes a higher IFN-γ serum levels than in other healthy or sick dogs breed [29]. The IFNG gene is located at chromosome 10 and presents four exons that codify a unique protein with 166 aminoacids.…”

Interleukin 6 and Interferon Gamma Haplotypes Are Related to Cytokine Serum Levels in Dogs in an Endemic <em>Leishmania infantum </em>Region

“…The IL-18, known as IFN-γ inducing factor, increases the production of this interferon by T cells and has a relevant role in the defense against visceral leishmaniasis [42,43]. According to that, these three cytokines (IFN-γ, IL-2 and IL-18) present high levels in Ibizan Hound dogs, which have a natural resistance against canine leishmaniasis [39,[44][45][46]. Our results indicate that these elevated levels are correlated with IL6-CGAAG haplotype which is found with a higher frequency in the Ibizan Hound dogs compared to Boxer ones.…”