Cytokine expression during the outcome of canine experimental infection by Leishmania infantum

Abstract

In this study, the cytokines, interferon-gamma (IFN-γ), interleukin-2 (IL-2), IL-12 p40, IL-6 and IL-10, expressed by peripheral blood mononuclear cells of 13 beagle dogs inoculated with Leishmania infantum amastigotes, were analysed during a period of up to 23 months. The course of infection was monitored through clinical and parasitological examinations, haematological alterations and serum antileishmania antibody levels. Dogs developed symptomatic infections with haematological alterations, humoral immune response and reduced specific lymphoproliferative response. Parasite presence was detected in bone marrow, popliteal lymph node and skin. Specifically stimulated cytokine transcripts were generally observed in a low proportion of dogs, except at months 9, 10 and 11 post-infection where there was a considerable increase in the proportion of dogs expressing IFN-γ and IL-2 mRNA. IL-12 p40 and IL-10 transcripts were sporadically detected in few animals. In non-infected animals, IFN-γ mRNA was the only detectable cytokine but only in cells cultured in the presence of concanavalin A (ConA). The low proportion of animals expressing specific cytokines, during the first 8 months of infection associated with evidences of parasite dispersion without clinical signs of disease, suggests the occurrence of a relatively “silent establishment” of the parasite avoiding adverse host-cell-mediated immunological reactions. The humoral immune response displayed in these animals, the cell-mediated immunosuppression, nor the disease severity could be related with the expression of IL-10. The predominance of a Th1 type response for a relatively short period indicates that these cytokines are required to control the infection delaying the appearance of progressive disease.