Plasmodium vivax recombinant vaccine candidate AMA-1 plays an important role in adaptive immune response eliciting differentiation of dendritic cells.
The Apical Membrane Antigen-1 (AMA-1) is a well-characterized and functionally important merozoite protein and is currently considered a major candidate antigen for a malaria vaccine. Previously, we showed that AMA-1 has an influence on cellular immune responses of malaria-naïve subjects, resulting in an alternative activation of monocyte-derived dendritic cells and induction of a pro-inflammatory response by stimulated PBMCs. Although there is evidence, from human and animal malaria model systems that cell-mediated immunity may contribute to both protection and pathogenesis, the knowledge on cellular immune responses in vivax malaria and the factors that may regulate this immunity are poorly understood. In the current work, we describe the maturation of monocyte-derived dendritic cells of P. vivax naturally infected individuals and the effect of P. vivax vaccine candidate Pv-AMA-1 on the immune responses of the same donors. We show that malaria-infected subjects present modulation of DC maturation, demonstrated by a significant decrease in expression of antigen-presenting molecules (CD1a, HLA-ABC and HLA-DR), accessory molecules (CD40, CD80 and CD86) and FcgammaRI (CD64) receptor (P < or = 0.05). Furthermore, Pv-AMA-1 elicits an upregulation of CD1a and HLA-DR molecules on the surface of monocyte-derived dendritic cells (P=0.0356 and P=0.0196, respectively), and it is presented by AMA-1-stimulated DCs. A significant pro-inflammatory response elicited by Pv-AMA-1-pulsed PBMCs is also demonstrated, as determined by significant production of TNF-alpha, IL-12p40 and IFN-gamma (P < or = 0.05). Our results suggest that Pv-AMA-1 may partially revert DC down-modulation observed in infected subjects, and exert an important role in the initiation of pro-inflammatory immunity that might contribute substantially to protection.
Bueno
Lilian Lacerda
LL
Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
Morais
Cristiane Guimarães
CG
Soares
Irene da Silva
IS
Bouillet
Leoneide Erica Maduro
LE
Bruna-Romero
Oscar
O
Fontes
Cor Jesus
CJ
Fujiwara
Ricardo Toshio
RT
Braga
Erika Martins
EM
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D006680:HLA Antigens / Q000096:biosynthesis; D006801:Humans; D016780:Malaria, Vivax / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D010966:Plasmodium vivax / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D015854:Up-Regulation
D015703:Antigens, CD; D000953:Antigens, Protozoan; D016207:Cytokines; D006680:HLA Antigens; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium