RESUMEN
In a murine model of experimental cutaneous leishmaniasis, we investigated the protection elicited by injection of histone H1 isolated from parasites by perchloric extraction, of a H1 recombinant protein produced in E. coli, and of H1 long and short synthetic peptides, against infection by L. major. Partial protection was achieved in most of the animals as shown by reduction in lesion size, upon immunization with histone H1 or its peptides, provided that the region 1-60 was present in the molecule. These observations argue in favor of a thorough examination of the possibility of including histone H1 described here in a cocktail vaccine against human leishmaniasis.
Asunto(s)
Histonas/inmunología , Leishmaniasis Cutánea/prevención & control , Vacunas Sintéticas , Animales , Modelos Animales de Enfermedad , Electroforesis en Gel de Poliacrilamida , Escherichia coli , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Proteínas Protozoarias/inmunologíaRESUMEN
Impairment of the Ag-presenting capacity of macrophages harboring intracellular Leishmania might represent one of the several mechanisms by which these parasites can evade host-protective T cell responses. Thus, the present study was designed to investigate the ability of macrophages, parasitized with Leishmania major, to present Ag to relevant T cell hybridomas. Results show that bone marrow-derived macrophages from BALB/c mice, after infection with L. major, have a greatly reduced capacity to present OVA, beta-galactosidase, and L. major-derived Ag to specific T cell hybrids derived from mice immunized with those Ag. In contrast, after pulsing with relevant peptide, macrophages containing L. major have a normal Ag-presenting capacity. The inhibition of presentation of native Ag did not appear to result from decreased endocytosis or catabolism. Inasmuch as the inhibition of presentation could not be attributed to an impaired processing of the Ag or an unavailability of MHC class II molecules on the surface of infected cells, these results could indicate that the presence of L. major interferes with the intracellular loading of MHC class II molecules with antigenic peptides.