Leishmania infantum LeIF and its recombinant polypeptides induce the maturation of dendritic cells in vitro: An insight for dendritic cells based vaccine

Abstract

We previously showed that recombinant Leishmania infantum eukaryotic initiation factor (LieIF) was able to induce the secretion of cytokines IL-12, IL-10 and TNF-α by human monocytes. In this study, we explored in vitro the potential of LieIF to induce phenotypic maturation and functional differentiation of murine bone-marrow derived dendritic cells (BM-DCs). Moreover, in order to identify potential immunnomodulatory regions of LieIF, eight recombinant overlapping protein fragments covering the whole amino acid sequence of protein, were constructed and assessed in vitro for their ability to induce maturation of BM-DCs. Our data showed that LieIF and some of its recombinant polypeptides were able to induce elevated expression of CD40, CD80 and CD86 co-stimulatory molecules with concurrent IL-12 production. Moreover, we used an in vivo experimental model of cutaneous leishmaniasis consisted of susceptible Leishmania major-infected BALB/c mice and we demonstrated that LieIF-pulsed-BM-DCs adoptively transferred in mice were capable to confer protection against a high dose parasite challenge. This study further describes the immunomodulatory properties of LieIF and its polypeptides bringing relevant information for their exploitation as candidate molecules for vaccine development against leishmaniasis.