Leishmania tarentolae as a potential disease-modifying agent in dogs infected with Leishmania infantum

Canine leishmaniosis (CanL), by Leishmania infantum, is a global zoonotic disease with complex immune interactions. The non-pathogenic Leishmania tarentolae emerged as a candidate for immunoprophylaxis, yet in vivo evidence demonstrating natural cross-protection in dogs remains scarce. This experimental study evaluated the immunological and clinical outcomes of co-exposure to both parasites. Fourteen purposedly breed dogs were allocated into three groups: Group 1 (G1) and Group 2 (G2) were previously exposed to L. tarentolae, then challenged with L. infantum intravenously (G1) or intradermally (G2). Group 3 (G3) served as unimmunized L. infantum-infected control group, with three dogs challenged intravenously and two intradermally. Animals were longitudinally monitored for 13.5 months through clinical, molecular and serological assessments. While prior exposure to L. tarentolae did not confer sterilizing immunity against L. infantum, differences in clinicopathological and immunological parameters were observed among experimental groups. Unimmunized controls (G3) developed higher UPC values during the later stages of the study, whereas pre-exposed dogs (G1 and G2) generally showed lower UPC values, although considerable inter-individual variability was observed. The intravenous challenge group (G1) developed high parasite burdens, hyperglobulinemia, and inflammatory alterations, whereas intradermally challenged group (G2) showed comparatively lower parasite burdens and fewer clinicopathological alterations. Additionally, in vitro stimulation with L. infantum, on peripheral blood monocytic cells from pre-immunized dogs, revealed a cytokine profile characterized by intermittent pro-inflammatory activation and variable regulatory interleukin-10 expression (IL-10). Overall, this is the first study detailing the longitudinal clinicopathological and immunological profile of L. infantum infection in the canine model, which suggests that prior exposure to L. tarentolae may influence the subsequent course of L. infantum. Hence, further studies are advocated to investigate the potential disease-modifying effect herein observed.