Characterization of immune system cells (mast cells, monocyto-macrophage derived cells, PBMC) obtained from peripherial blood, bone marrow, spleen, lymphonode biopsies in humans (HIV positive or negative) and dogs infected by Leishmania spp:a key diagnostic and therapeutic approaches

Leishmaniasis is one of the most important infectious diseases worldwide. Currently, 12 million people in 88 (mostly develo- ping) countries are infected with ~2 million new infections per year. 60.000 annual deaths result from leishmaniasis. A vacci- ne does not exist at present and some treatment options are expensive and can cause major side effects (Scott et al., Immunol. Rev. 2004, 201:318-338). The disease is caused by an obligate intracellular parasite inoculated into the skin by the bite of a sand fly. Humans as well as small animals and dogs are natural reservoirs for the parasite. Visceral leishmaniasis (VL) is a li- fe threatening disease characterized by uncontrolled parasitisation of spleen, liver, and bone marrow. The mechanisms under- lying the failure to control the growth and systemic spread of leishmania parasites in VL are not well understood. While the absence of antigen-specific Th1 responses in PBMC from VL patients is thought to be casually related to disease progression, the finding that these patients also express elevated IFNgamma mRNA in lesional tissue, as well as elevated serum levels of pro-inflammatory cytokines suggests that their immunologic defect cannot be simply explained by immune tolerance or Th2 polarization. As a possible homeostatic mechanism to control persistent infection-induced inflammation, elevated levels of regulatory cytokines IL-10 have repeatedly been reported in clinical studies of VL (Nylén and Sacks, Trends in Immunol. 2007, 28:378-384). VL, caused by the protozoan parasite Leishmania infantum, is a sand fly-borne disease found in the Me- diterranean area, Asia, and Latin America . In most of this range, the domestic dog is the main reservoir host (Gramiccia and Gradoni, Int. J. Parasitol. 2005, 35: 1169-1180; Dantas-Torres F., Vet. Parasitol. 2007, 149:139-146). Dogs may suffer from a severe disease characterized by chronic evolution of viscero-cutaneous signs, which occurs in fewer than 50% of infected animals; however, both asymptomatic and symptomatic dogs can be infectious to phlebotomine vectors. Canine leishmaniasis (CL) is a major veterinary and public health problem in traditional areas of endemicity, but also in areas where the disease is not endemic but outbreaks are occasionally reported, such as in the United States and Canada and northern Europe.