Cellular and humoral immune responses in dogs experimentally and naturally infected with Leishmania infantum

In this paper we describe a number of immunological parameters for dogs with a chronic Leishmania infantum infection which exhibit patterns of progressive disease or apparent resistance. The outcome of infection was assessed by isolation of parasites, serum antibody titers to Leishmania antigen, and development of clinical signs of leishmaniasis. Our studies show that 3 years after experimental infection, asymptomatic or resistant dogs responded to L. infantum antigen both in lymphocyte proliferation assays in vitro and in delayed-type hypersensitivity reaction, whereas no serum antibodies to parasite antigen were shown. In contrast, symptomatic or susceptible animals failed to respond to parasite antigen in cell-mediated assays both in vitro and in vivo and showed considerably higher serum antibodies to leishmanial antigens. In addition, significantly higher level of interleukin 2 (IL-2) and tumor necrosis factor were found in supernatants from stimulated peripheral mononuclear cells from asymptomatic dogs compared with those from symptomatic and control uninfected dogs. IL-6 production did not vary significantly among the groups studied. Finally, we observed similar results with a group of mixed-breed dogs with natural Leishmania infections also grouped as asymptomatic or symptomatic on the basis of clinical signs of canine visceral leishmaniasis. These results demonstrate that serum antibody titers, antigen-specific proliferative responses, delayed-type hypersensitivity skin reactions, and IL-2 and tumor necrosis factor production by peripheral mononuclear cells can be used as markers of disease progression.