Role of mononuclear phagocytes in elimination of Plasmodium chabaudi AS infection

Abstract

The role of mononuclear phagocytes in acquired immunity resulting in the intraerythrocytic destruction and elimination of malarial parasites was investigated in the murine model of infection with Plasmodium chabaudi AS. Mice were treated 1 day before or 6 days after infection with agents which either result in augmentation or activation of the non-specific, microbicidal effector function of mononuclear phagocytes or in depletion of cells of this lineage. To examine the effect of agents which activate mononuclear phagocytes. A/J mice, which are susceptible to P. chabaudi AS and exhibit fulminant parasitaemia and death within 10 days of intraperitoneal infection with 10(6) P-RBC, were treated intravenously with muramyl dipeptide (MDP) or liposome-encapsulated MDP-glycerol dipalmitate (MDP-GDP). Treatment administered 1 day before infection was ineffective. Treatment on day 6 post-infection with liposome-encapsulated MDP-GDP (1 microgram) resulted in a significant decrease in parasitaemia on day 8 and survival, while treatment with free MDP (100 micrograms) resulted only in a significant decrease in parasitaemia. To examine the effect of depletion of mononuclear phagocytes, C57BL/6 mice, which are resistant to P. chabaudi AS infection and eliminate the parasite by 4 weeks, were treated intravenously with 3 mg silica. Silica administered 1 day before or 6 days post-infection abrogated resistance resulting in a delay in elimination of the parasite and host mortality. Treatment on day 6 was more effective, with death by day 13 post-infection of 70% of the normally resistant C57BL/6 mice which exhibited fulminant parasitaemia levels. These results thus provide in-vivo evidence that mononuclear phagocytes play a critical role in the elimination of infection with the murine malaria species P. chabaudi AS. Furthermore, these results suggest that the time of administration of agents which alter mononuclear phagocyte function may be important in determining their effect on host antimalarial defences.