Dendritic Cells Induce Immunity and Long-Lasting Protection against Blood-Stage Malaria despite an In Vitro Parasite-Induced Maturation Defect

DOI Web Site 3 Citations
  • Dodie S. Pouniotis
    Vaccine and Infectious Diseases Unit, The Austin Research Institute, Heidelberg, Victoria, Australia
  • Owen Proudfoot
    Vaccine and Infectious Diseases Unit, The Austin Research Institute, Heidelberg, Victoria, Australia
  • Violeta Bogdanoska
    Vaccine and Infectious Diseases Unit, The Austin Research Institute, Heidelberg, Victoria, Australia
  • Vasso Apostolopoulos
    Vaccine and Infectious Diseases Unit, The Austin Research Institute, Heidelberg, Victoria, Australia
  • Theodora Fifis
    Vaccine and Infectious Diseases Unit, The Austin Research Institute, Heidelberg, Victoria, Australia
  • Magdalena Plebanski
    Vaccine and Infectious Diseases Unit, The Austin Research Institute, Heidelberg, Victoria, Australia

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>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-γ) 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<jats:italic>Plasmodium yoelii</jats:italic>or<jats:italic>Plasmodium chabaudi</jats:italic>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-γ-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.</jats:p>

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