Adoptive transfer of dendritic cells pulsed with Leishmania infantum nucleosomal histones confers protection against cutaneous leishmaniosis in BALB/c mice.
The mechanisms underlying the protective effects induced by dendritic cells (DC)-based vaccines against Leishmania major in mice are not yet completely understood. In the present study, we investigated the potential of DC loaded with a mixture of the Leishmania infantum histones in the absence (HIS-pulsed DC) or presence of CpG motifs (HIS+CpG-pulsed DC) as a candidate vaccine against cutaneous leishmaniosis. Our data showed that a single intravenous administration of HIS-pulsed DC or HIS+CpG-pulsed DC confers control to L. major infection in BALB/c mice. Interestingly, all HIS-pulsed DC vaccinated mice remained susceptible to a second challenge. We found that the efficient immunity in BALB/c mice was associated to a Th1 response and a restriction of Th2 type of response upon challenge with L. major parasites. More importantly, the anti-leishmanial immunological mechanisms of protection were dependent on the ability to induce a low frequency of Foxp3(+) regulatory T cells at the site of infection. These results document that a vaccine based on a HIS+CpG-pulsed DC formulation may be as efficient for vaccination as one based on L. major antigen (Lm)+CpG-pulsed DC. Thus, HIS+CpG-pulsed DC may prove to be a new and further tool to add to those designed.
Carrión
Javier
J
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, E-28049 Spain. jcarrion@cbm.uam.es
Nieto
Ana
A
Soto
Manuel
M
Alonso
Carlos
C
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D003713:Dendritic Cells; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006657:Histones / Q000008:administration & dosage; D007275:Injections, Intravenous; D018314:Leishmania infantum / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D015800:Protozoan Proteins / Q000008:administration & dosage; D016052:Protozoan Vaccines / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006657:Histones; D009838:Oligodeoxyribonucleotides; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins