Susceptibility of different strains of mice to hepatic infection with Plasmodium berghei

Abstract

Despite the low susceptibility of BALB/c mice to hepatic infection by Plasmodium berghei, this animal model is routinely used to investigate the basic biology of the malaria parasite and to test vaccines and the immune response against exoerythrocytic (EE) stages derived from sporozoites. A murine model in which a large number of EE parasites are established would be useful for furthering such investigations. Therefore, we assayed six mouse strains for susceptibility to erythrocytic and hepatic infections. The administration of 50 sporozoites by intravenous inoculation was suflicient to establish erythrocytic infections in five of five C57BL/6 mice compared with 10,000 sporozoites required to infect 100%/ of BALB/c mice. To assay for hepatic infections, mice received an intravenous inoculum of 106 sporozoites, and liver sections for light microscopy and histology were obtained at 29 and 44 h postinoculation. EE parasites were visualized by immunofluorescence, using an antibody to a P.fakciparum heat shock protein. The mean number of EE parasites per 100 cm2 for C57BL/6 and A/J strains was significantly higher than that for BALB/c (2,190 260, 88 38, and 6 2, respectively). The proportion of inoculated sporozoites transforming into liver schizonts was 8.2% in C57BL/6 and <1% in C3HVHeJ, DBA/1, and Swiss CD-1/ICR mice. Nonspecific inflammatory infiltrates around EE parasites were less prevalent in liver sections from C57BL/6 mice than in those from BALB/c mice, which contributed to the decrease in developing EE stages in BALB/c mice. These data indicate that the C57BL/6-P. berghei system is preferable for investigating the biology and immunology of liver stage parasites.

Characterization of the Plasmodium falciparum and P. berghei glycerol 3‐phosphate acyltransferase involved in FASII fatty acid utilization in the malaria parasite apicoplast

“…Selecting Pb apiG3PAT (À) clone 1 for further analysis, we then compared time to patency with wild type after injection of 1000 or 10 000 sporozoites in six independent experiments. Similar to previous experiments with outbred mice (Jaffe et al, 1990;Scheller et al, 1994), injection of 10 000 wild type sporozoites produced infections in all six mice after an average of 4.2 days, while injection of 1000 wild type sporozoites produced infections in four mice after an average of 5.8 days (Table 1). By comparison, injection of either dose of Pb apiG3PAT (À) sporozoites produced infections in a smaller fraction of mice and with substantial delays (4-5 days) relative to wild type (Table 1).…”

Experimental Determination of the Force of Malaria Infection Reveals a Non-Linear Relationship to Mosquito Sporozoite Loads

“…Indeed, 2 to 4 P. yoelii sporozoites inoculated intravenously (IV) initiate malaria infection in 50% of mice [12][13][14], while 10 P. vivax or P. cynomolgi sporozoites initiated infection in 100% of human volunteers or rhesus monkeys, respectively [15,16]. This is in contrast to another rodent malaria model, Plasmodium berghei where ID50 values are 50 to 1,000 times higher [17,18]. Experiments in which sporozoites are inoculated by P. yoelii and P. falciparum infected mosquitoes found that in both cases, 5 infected mosquito bites are required to infect 100% of mice or human subjects, respectively [14,19,20].…”

Liver stage malaria infection is controlled by host regulators of lipid peroxidation

“…Previous literature highlights the importance of host cell variation, which can drastically alter susceptibility to infection. In one study using the rodent malaria species Plasmodium berghei, the number of sporozoites required to initiate blood stage infection varied from 50 to 10,000 across different strains of naive mice [3]. We have demonstrated that some differences in infectivity originate from differences in hepatocyte biology [4], suggesting that variation in the host can drastically alter susceptibility to infection.…”