Dendritic cells induce immunity and long-lasting protection against blood-stage malaria despite an in vitro parasite-induced maturation defect.
Dendritic cells (DC) suffer a maturation defect following interaction with erythrocytes infected with malaria parasites and become unable to induce protective malaria liver-stage immunity. Here we show that, by contrast, maturation-arrested DC in vitro are capable of the successful induction of antigen-specific gamma interferon (IFN-gamma) and interleukin 4 (IL-4) T-cell responses, antibody responses, and potent protection against lethal blood-stage malaria challenge in vivo. Similar results were found with DC pulsed with intact parasitized Plasmodium yoelii or Plasmodium chabaudi erythrocytes. Cross-strain protection was also induced. High levels of protection (80 to 100%) against lethal challenge were evident from 10 days after a single immunization and maintained up to 120 days. Interestingly, correlation studies versus blood-stage protection at different time points suggest that the immune effector mechanisms associated with protection could change over time. Antibody-independent, T-cell- and IL-12-associated protection was observed early after immunization, followed by antibody and IL-4-associated, IFN-gamma-independent protection in long-term studies. These results indicate that DC, even when clearly susceptible to parasite-induced maturation defect effects in vitro, can be central to the induction of protection against blood-stage malaria in vivo.
Vaccine and Infectious Diseases Unit, The Austin Research Institute, Austin Campus Heidelberg, Victoria 3084, Australia.
Dodie S
DS
Pouniotis
Owen
O
Proudfoot
Violeta
V
Bogdanoska
Vasso
V
Apostolopoulos
Theodora
T
Fifis
Magdalena
M
Plebanski
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines; D051379:Mice; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi / Q000276:immunology / Q000472:pathogenicity*; D010967:Plasmodium yoelii / Q000276:immunology / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma