El papel de las células dendríticas es fundamental en la señalización de la infección por Leishmania desde la piel hasta los ganglios linfáticos; sin embargo, la proliferación de Leishmania en estas células está restringida. En el macrófago, célula hospedera de Leishmania por excelencia, los parásitos proliferan irrestrictamente y el control de la infección depende directamente de los niveles de óxido nítrico. Debido a que la disponibilidad de hierro celular modula la actividad de la enzima óxido nítrico sintetasa del macrófago y para analizar las causas de la restricción de la proliferación de Leishmania en células dendríticas, en este trabajo evaluamos la influencia del hierro libre intracelular sobre la funcionalidad de células de dendríticas y la infección por Leishmania major. Los resultados demuestran que la en células de Langerhans de la piel expuestas a quelantes de hierro la infección por Leishmania major y la expresión del receptor de transferrina disminuyen, sin alterar la producción de óxido nítrico y otras propiedades funcionales de la célula. La incubación de células dendríticas de médula ósea con quelantes de hierro no afecta la infección por Leishmania major ni la producción de óxido nítrico de la célula. Estos resultados demuestran que la restricción de la proliferación de Leishmania en células dendríticas es independiente de los niveles de hierro celular y de los niveles de óxido nítrico.

The immune changes associated to the experimental infection of mice with Leishmania major and the leading role played by the Langerhans cells in the signalling of the infection from the skin up to the lymphatic ganglions are well known; however, the physiological mechanisms that restrict parasite proliferation in these cells have not been yet identified. In macrophages, control of infection is associated with nitric oxide production. The availability of cellular iron modulates this effector’s system, including the activity of the enzyme nitric oxide synthase. Herein, and in an attempt to analyze if the iron metabolism- nitric oxide synthase expression loop described in other immune cells is present in dendritic cells, we have analyzed the effect of iron chelators as deferroxamine and pyridoxal-isoniconoyl hidrazone on different functions of dendritic cells isolated from BALB/c mice bone marrow. The results suggest that the control of Leishmania infection in dendritic cells is independent of the iron metabolism- nitric oxide synthase expression loop.

We have demonstrated that Leishmania spp. grown as promastigotes, are sensitive to the K+ channel inhibitors 4-aminopyridine and glibenclamide. Their host cells, the macrophages, are not affected by similar concentrations of the drugs. We have also initiated the molecular characterization of the mechanisms involved in the development of drug resistance to glibenclamide by the parasite. Therefore, we have selected experimentally and begun to characterize the Venezuelan Leishmania (Leishmania) strain, NR resistant to glibenclamide [NR(Gr)]. The analysis of genomic DNA evidenced the existence of a fragment which apparently is amplified in NR(Gr). The fragment recognized by the pgpA probe, related to the Leishmania P-glycoprotein family and which was originally isolated from L. tarentolae, showed a size polymorfism between the sensitive and the resistant strain. These results suggest that the development of resistance to glibenclamide in the strain NR(Gr) might be associated with the amplification of the ltpgpA or related gene(s)