Toll-Like Receptors 2, 4, and 7, Interferon-Gamma, Interleukin 10, and Programmed Death Ligand 1 Transcripts in Leishmanin Skin Test-Positive Reactions of Ibizan Hound Dogs

Abstract

The leishmanin skin test (LST) is an in vivo technique commonly used to evaluate the Leishmania-specific cellular immune response in dogs. However, information regarding the local immune response in LST-positive reactions is scarce. We examined the pattern of toll-like receptor 2 (TLR2), TLR4, TLR7, interleukin- (IL-) 10, interferon gamma (IFN-γ), and (program death ligand) PD-L1 gene expression in LST-positive reactions and paired normal-looking skin of nine infected Ibizan hound dogs. Healthy skin from ten seronegative dogs from a nonendemic area was analysed as a negative control. Immune gene expressions were examined by quantitative PCR (qPCR) analysis. LST-positive reactions presented significant upregulation of TLR2, TLR4, IL-10, IFN-γ, and PD-L1 and downregulation of TLR7 when compared with healthy skin of seronegative control dogs from a nonendemic area. All transcripts but TLR7 were significantly higher in LST-positive reaction than in paired normal-looking skin of Ibizan hound. The expression profile of immune genes in LST-positive reactions was similar to that previously observed in clinically lesioned skin of mildly diseased dogs with papular dermatitis due to Leishmania infantum infection. This data provide additional support for the important role of TLRs in canine leishmaniosis.

Canine Cytokines Profile in an Endemic Region of L. infantum: Related Factors

“…This response makes it possible to control the infection, and it is known as a protective response, since the host does not show clinical signs of the disease [19]. In fact, elevated serum levels of IFN-γ are related with low parasite counts and few or no clinical signs compared to sick dogs [20], and these levels increase with anti-Leishmania treatment together with clinical improvement and low blood parasitemia [21,22]. Infected dogs exhibit increases in serum levels of IFN-γ, IL-6, and IL-18 and decreases in TNF-α, IL-2, and IL-8 compared to non-infected dogs [23].…”

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

“…The activation of macrophages by IFN-γ has been associated with effective T helper 1 (Th1) cellular immunity, and related to elimination of intracellular amastigotes and the control of the disease [24]. In Ibizan hound dogs, Ordeix et al ( 2020) observed high expression levels of IFN-γ in skin samples of leishmanin skin test (LST) positive than in healthy skin from control dogs of nonendemic area [27]. Previously, this upregulation of IFN-γ has been correlated with low severity of disease [28].…”

“…The ability of the host to control Leishmania infection requires a strong cellular immune response, associated with the activation of T helper (Th)-1 cells producing IFN-γ, and IL-2 [32,33]. Some studies about the rst two noticed their relationship with a control and a protective response against Leishmania infection by the host [34][35][36]. Aslan et al (2016) found that IL-2 expression was negatively correlated with splenic parasite loads in experimentally infected dogs [37].…”

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

“…Regarding L. infantum, the control of infection requires the activation of T helper 1 (Th-1) cells, which increases the IFN-γ and IL-2 serum levels [37,38]. The production of these cytokines was correlated with resistance to disease, so IFN-γ has been proposed as biomarker for immune monitoring in canine leishmaniasis [17,39,40], and IL-2 expression was negatively correlated with splenic parasite loads in infected dogs [41]. 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].…”