title: 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.
abstract: 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 IFNγ, 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 IFNγ against IL-10, the absence of TGF-β 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.
authors.affiliation: Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias Ave., 115 21 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Agallou
authors.forename: Maritsa
authors.initials: M
authors.lastname: Margaroni
authors.forename: Evdokia
authors.initials: E
authors.lastname: Karagouni
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000097:blood; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008099:Liver / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000276:immunology*; D012376:Rodent Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D013154:Spleen / Q000469:parasitology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; C408982:CPG-oligonucleotide; D016207:Cytokines; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D015800:Protozoan Proteins