Journal Article

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

Agallou, Maria, Margaroni, Maritsa, Karagouni, Evdokia

2011

Overview

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-1112–31aa 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-1112-31aa 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-1112–31aa peptide-pulsed BM-DCs, they exhibited only partial protection against Leishmania infantum challenge, whereas (KMP-1112–31aa 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.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Adjuvants, Immunologic - pharmacology / Adoptive Transfer - methods / Allergy and Immunology / animal models / animal organs / Animals / antibodies / Antibodies, Protozoan - blood / antigens / Applied microbiology / Biological and medical sciences / Bone marrow / CpG ODNs / Cytokines - secretion / DCs-based vaccine / dendritic cells / Dendritic Cells - immunology / Disease Models, Animal / Fundamental and applied biological sciences. Psychology / Human protozoal diseases / IFNγ / IgG1 / IgG2a / IL-10 / IL-12 / IL-17 / Immune response / Immune system / immunoglobulin G / Immunoglobulin G - blood / Infections / Infectious diseases / interleukin-10 / interleukin-12 / interleukin-17 / KMP-11 / Leishmania infantum / Leishmania infantum - immunology / Leishmaniasis, Visceral - immunology / Leishmaniasis, Visceral - pathology / Leishmaniasis, Visceral - prevention & control / Leshmaniasis / Liver - parasitology / Medical sciences / Membrane Glycoproteins - immunology / membrane proteins / Mice / Mice, Inbred BALB C / Microbiology / Murine visceral leishmaniasis / oligodeoxyribonucleotides / Oligodeoxyribonucleotides - pharmacology / parasite load / Parasites / Parasitic diseases / phenotype / Protozoal diseases / Protozoan Proteins - immunology / Rodent Diseases - immunology / Rodent Diseases - pathology / Rodent Diseases - prevention & control / screening / Spleen - parasitology / TGF-β / transforming growth factor beta / vaccination / Vaccines / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) / Vector-borne diseases / visceral leishmaniasis