Final Activity Report Summary - MALISTA (Malaria liver stages: characterization of essential genes for novel intervention strategies.)
Plasmodium parasites, the causative agents of malaria, have a complex life cycle that alternates between a mosquito vector and a vertebrate host. Infected mosquitoes transmit plasmodium forms called sporozoites, which rapidly migrate to the host liver, invade hepatocytes and differentiate into replicative liver stages (LS). After intensive multiplication, LS release merozoites that invade erythrocytes and cause malaria symptoms. Plasmodium LS are clinically silent and represent ideal targets for prophylactic antimalarial drug and vaccine interventions. However, the molecular mechanisms underlying LS development remain poorly characterised.
The aim of this project was to characterise genes involved during LS development. We identified a plasmodium protein, termed SLARP, which was specifically expressed in sporozoites and LS. In the absence of SLARP, sporozoites invaded host cells normally but were then completely arrested at a very early stage of LS development. Our results indicated that SLARP functioned as a specific regulator of the expression of genes involved in LS replication. Interestingly, early arrested SLARP-deficient parasites conferred only limited protection in immunised mice, suggesting a requirement of parasite maturation to induce optimal protective immune responses against LS. Our study provided new insights into gene expression regulation during the complex life cycle of the malaria parasite and had important implications for the design of vaccines targeting plasmodium liver stages.
The aim of this project was to characterise genes involved during LS development. We identified a plasmodium protein, termed SLARP, which was specifically expressed in sporozoites and LS. In the absence of SLARP, sporozoites invaded host cells normally but were then completely arrested at a very early stage of LS development. Our results indicated that SLARP functioned as a specific regulator of the expression of genes involved in LS replication. Interestingly, early arrested SLARP-deficient parasites conferred only limited protection in immunised mice, suggesting a requirement of parasite maturation to induce optimal protective immune responses against LS. Our study provided new insights into gene expression regulation during the complex life cycle of the malaria parasite and had important implications for the design of vaccines targeting plasmodium liver stages.