Figure 1.
Analysis of wild type and Δmsp7 mutant parasites in acute infection or semi-immune mouse models.
(A) For acute infection, all 6–8 week old mice were given inocula of 1000 infected RBCs of the respective parasite lines and monitored every other day by thin blood film. *Day 10 is based on data from 5 mice, while all other days are based on data from 10 mice (SEM shown). (B) Semi-immune mouse model showing the average parasitemia of wild type and Δmsp7 P. berghei infected mice immediately before drug cure in cycles 4 and 5 of the infection-cure protocol (SEM shown).
Figure 2.
Aged rat model for anemia and death.
(A) SMA model for aged rats, showing average percent of baseline Hb and average parasitemia. (B) Number of rats that survived in the aged rat model. The data are from three experiments, N = 30 rats. (C) Comparison of percent parasitemia (%P), percent hemoglobin drop (%Hb), and death (#Death) in naïve rats infected with wild type parasites (black bars) and rats previously infected with Δmsp7 parasites and then re-infected with wild type parasites (gradient bars).
Figure 3.
Mass and histological analysis of the rat spleen during infection.
(A) Comparison of spleen mass on days 8 and 10 of infection. (B) H&E stained formalin-fixed paraffin embedded spleen sections from uninfected rats and rats infected with P. berghei wild type or Δmsp7 at day 8 p.i. Representative follicles and germinal centers are shown. The greatest size increase is seen in infections with Δmsp7 (B3). There is disappearance of the marginal zone (MZ) in both wild type and mutant parasite-infected rats (B2&B3). There is infiltration (multiplication) of nucleated cells within the red pulp (RP) (B2&B3). (C) Quantitative analysis of spleen follicle size from uninfected and infected (wild type and Δmsp7) rats on day 8 post-infection. For each rat, the size of follicles was analyzed in four different spleen sections. In total, 75 and 81 spleen follicles were analyzed for uninfected rats (n = 4) and rats infected either with wild type (n = 3) or Δmsp7 mutant (n = 4) parasites, respectively. Scales represent standard error of the means. T, trabecula; RP, red pulp; GC, germinal center; CA, central artery; F, follicle; TV, trabecular vein; MS, marginal sinus; MZ, marginal zone; PALS, periarteriolar lymphoid sheaths. Original magnification, x100.
Figure 4.
Rats were infected and monitored for parasitemia and Hb levels until day 8 or 10 post-infection, at which point they were exsanguinated and plasma was isolated. Interferon-gamma induced protein 10 (IP-10); macrophage inflammatory protein-beta (MIP-1beta) and myeloperoxidase appear to be elevated on Day 8 in wild type-infected animals relative to mutant-infected animals. However, when we adjusted for the number of tests realized, P-values for IP-10, MIP-1beta, and myeloperoxidase all were >0.05. N = 3 wild-type; N = 4 Δmsp7.