Abstract
BackgroundImmunity to malaria requires innate, adaptive immune responses and Plasmodium-specific memory cells. Previously, mice semi-immune to malaria was developed. Three cycles of infection and cure (‘three-cure’) were required to protect mice against Plasmodium berghei (ANKA strain) infection.MethodsC57BL/6 J mice underwent three cycles of P. berghei infection and drug-cure to become semi-immune. The spleens of infected semi-immune mice were collected for flow cytometry analysis. CD11c(+) cells of semi-immune mice were isolated and transferred into naïve mice which were subsequently challenged and followed up by survival and parasitaemia.ResultsThe percentages of splenic CD4(+) and CD11c(+) cells were increased in semi-immune mice on day 7 post-infection. The proportion and number of B220(+)CD11c(+)low cells (plasmacytoid dendritic cells, DCs) was higher in semi-immune, three-cure mice than in their naïve littermates on day 7 post-infection (2.6 vs 1.1% and 491,031 vs 149,699, respectively). In adoptive transfer experiment, three months after the third cured P. berghei infection, splenic CD11c(+) DCs of non-infected, semi-immune, three-cure mice slowed Plasmodium proliferation and decreased the death rate due to neurological pathology in recipient mice. In addition, anti-P. berghei IgG1 level was higher in mice transferred with CD11c(+) cells of semi-immune, three-cure mice than mice transferred with CD11c(+) cells of naïve counterparts.ConclusionCD11c(+) cells of semi-immune mice protect against experimental cerebral malaria three months after the third cured malaria, potentially through protective plasmacytoid DCs and enhanced production of malaria-specific antibody.
Highlights
Immunity to malaria requires innate, adaptive immune responses and Plasmodium-specific memory cells
The entire set of experiments was performed at least twice. This is the first study demonstrating that splenic CD11c(+) cells from semi-immune mice are capable of prolonged inhibition of malaria parasite development and prevention of experimental cerebral malaria (ECM)
This semi-immune mouse model was developed by repeated infection and radical anti-malaria treatment, mimicking the natural boost infection and recovery in humans in areas of intense P. falciparum transmission
Summary
Immunity to malaria requires innate, adaptive immune responses and Plasmodium-specific memory cells. Immunity to malaria in humans is a step-wise process that spans invasion of sporozoites into the body to development of erythrocytic parasites. This process involves humoral and cellular responses of innate immune cells (e.g., macrophages, dendritic cells (DCs)) and adaptive IFN-γ-producing CD4(+) and CD8(+) T cells [1]. Memory CD8(+) T cells specific for Plasmodium liver-stage antigens prolong protection against malaria [4]. Both antibody and memory B cell responses to malarial antigens
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