Cellular vaccination with bone marrow-derived dendritic cells pulsed with a peptide of Leishmania infantum KMP-11 and CpG oligonucleotides induces protection in a murine model of visceral leishmaniasis

摘要

The use of dendritic cells (DCs) pulsed with defined Leishmania antigens could be a potential immune intervention tool for the induction of protection against infection. In the present study, bone marrow-derived DCs (BM-DCs) pulsed ex vivo with the peptide 12-31aa portion of kinetoplastid membrane protein (KMP)-11 (KMP-11(12-31aa) peptide) acquired a semimature phenotype expressing IL-12 and IL-10, whereas pulsing with the combination of the peptide and CpG oligodeoxynucleotides (ODNs) resulted in their functional maturation expressing mainly IL-12. Vaccination of genetically susceptible to parasite BALB/c mice with both peptide-pulsed BM-DCs elicited a peptide-specific mixed Th1/Th2 immune response, characterized by the production of IFN gamma, IL-10 and IgG1 and IgG2a isotype antibodies. However, only BM-DCs pulsed with the combination of KMP-11(12-31aa) peptide and CpG ODNs induced the differentiation of peptide-specific Th17 cells, indicating the adjuvanticity of CpG ODNs. When BALB/c mice were vaccinated with KMP-11(12-31aa) peptide-pulsed BM-DCs, they exhibited only partial protection against Leishmania infantum challenge, whereas (KMP-11(12-31aa) peptide + CpG ODNs)-pulsed BM-DCs reduced efficiently the parasite load in visceral organs. Protective immunity was correlated with restoration of lymphoproliferative responses and a modulation of parasite-specific cellular responses towards Th1 and Th17 profile, confirmed by the isotype switching towards IgG2a, the enhanced production of IFN gamma against IL-10, the absence of TGF-beta and the overproduction of IL-17. Thus, ex vivo antigen-pulsed BM-DCs represent a powerful tool for the study of protective immune responses against leishmanial infection. Moreover, these findings suggest the use of BM-DCs as effective tools in antigen and adjuvant screening in the design of a protective vaccine against leishmaniasis and other pathogen-related infections