RESUMEN
We investigated the functional role of the Leishmania histone H1 and demonstrate for the first time that addition of histone H1 has a strong effect on microccocal digestion, chromatin condensation of parasite nuclei and that its overexpression can modulate parasite infectivity in vivo.
Asunto(s)
Cromatina/metabolismo , Histonas/fisiología , Leishmania major/fisiología , Leishmaniasis Cutánea/parasitología , Animales , Línea Celular , Expresión Génica , Histonas/genética , Leishmania major/química , Leishmania major/patogenicidad , Macrófagos/parasitología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Transducción de Señal , Transfección , VirulenciaRESUMEN
Triggering the maturation of dendritic cells (DC) with toll-like receptor (TLR) agonists is a favored strategy for the development of vaccine adjuvants. The triacyl pseudo-dipeptidic agent OM-197-MP-AC mimicking the lipid A structure of endotoxin induces the maturation of human monocyte-derived DC. In this study we investigated the signaling pathway by which this molecule activates DC. The ability of OM-197-MP-AC to induce maturation of human and mouse DC and macrophages was dependent on TLR4, not TLR2. Ovalbumin-specific humoral and T helper cell responses were significantly augmented by OM-197-MP-AC treatment. Taken together these results indicate that OM-197-MP-AC is a TLR4 agonist inducing DC maturation and represents a novel class of vaccine adjuvants devoid of the known pyrogenic effects associated with classical LPS derivatives.