Plasmodium berghei: eosinophilic depression of infection in mice

The effects of eosinophilia on the course of Plasmodium berghei infection in mice were studied. Eosinophilia was induced by intravenous injection of Ascaris suum body fluid into the mice. Results indicated that eosinophils may play a role in the suppression of murine malaria. A significant reduction in parasitemias and increased survival time in eosinophilic mice occurred compared to mice not treated with A. suum body fluid. Reduction of parasitemia was effectively achieved when the mice were challenged with P. berghei, only after the level of eosinophils reached at least 10% of total white cell counts in the circulation. These findings may offer an additional explanation for the suppression of malaria in individuals with severe ascariasis.     

Oral artesunate prevents Plasmodium berghei Anka infection in mice

Artesunate, a semi-synthetic derivative of a naturally occurring anti-malarial artemisinin was compared with chloroquine in C57BL/6 mice infected with Plasmodium berghei Anka (PbA). A 7-day oral administration of artesunate prevented parasitaemia at 10 mg/kg/day. However, recrudescence of parasitaemia and cerebral malaria occurred upon cessation of treatment followed by death within 28 days. However, a 14-day course of artesunate (100 mg/kg/day) prevented completely the development of parasitaemia and cerebral malaria with a survival of more than 60-days as did 10 mg/kg/day chloroquine. These data demonstrate that oral artesunate inhibits PbA and prevents cerebral malaria, but needs to be administered at high dose and for prolonged time to eradicate PbA infection in mice.     

Direct infection of hepatocytes by sporozoites of Plasmodium berghei

To identify the unknown liver cell type initially invaded by sporozoites of mammalian malaria, young rats were inoculated intravenously with large numbers of Plasmodium berghei sporozoites obtained from infected Anopheles stephensi mosquitoes. Fine structural studies of liver specimens obtained from the rats within 2 min after inoculation demonstrated the presence of morphologically unaltered sporozoites in the cytoplasm of hepatocytes. Many sporozoites were also observed undergoing cytolysis within the lysophagosomes of Kupffer cells, as well as other phagocytic cells. These observations strongly suggest direct infection of the hepatocyte by the sporozoite.     

Intravital observation of Plasmodium berghei sporozoite infection of the liver

Plasmodium sporozoite invasion of liver cells has been an extremely elusive event to study. In the prevailing model, sporozoites enter the liver by passing through Kupffer cells, but this model was based solely on incidental observations in fixed specimens and on biochemical and physiological data. To obtain direct information on the dynamics of sporozoite infection of the liver, we infected live mice with red or green fluorescent Plasmodium berghei sporozoites and monitored their behavior using intravital microscopy. Digital recordings show that sporozoites entering a liver lobule abruptly adhere to the sinusoidal cell layer, suggesting a high-affinity interaction. They glide along the sinusoid, with or against the bloodstream, to a Kupffer cell, and, by slowly pushing through a constriction, traverse across the space of Disse. Once inside the liver parenchyma, sporozoites move rapidly for many minutes, traversing several hepatocytes, until ultimately settling within a final one. Migration damage to hepatocytes was confirmed in liver sections, revealing clusters of necrotic hepatocytes adjacent to structurally intact, sporozoite-infected hepatocytes, and by elevated serum alanine aminotransferase activity. In summary, malaria sporozoites bind tightly to the sinusoidal cell layer, cross Kupffer cells, and leave behind a trail of dead hepatocytes when migrating to their final destination in the liver.     

Dendritic cells subsets mediated immune response during Plasmodium berghei ANKA and Plasmodium yoelii infection

The roles of dendritic cells (DCs) in mediating immunity against Plasmodium infection have been extensively investigated, but immune response during pathogenesis of malaria is still poorly understood. In the present study, we compared the splenic DCs phenotype and function during P. berghei ANKA (PbA) or P. yoelii (P. yoelii) infection in Swiss mice. We observed that PbA-infected mice developed more myeloid and mature DCs capable of secreting IL-12, while P. yoelii-infected mice had more plasmacytoid and immature DCs secreting higher levels of IL-10. Expression of FoxP3, IL-17, TGF-β and IL-6 were also different between these two infections. Thus, these results suggest that the phenotypic and functional subsets of splenic DCs are key factors for regulating immune responses to PbA and P. yoelii infections.