The contribution of Plasmodium chabaudi to our understanding of malaria

Abstract

Malaria kills close to a million people every year, mostly children under the age of five. In the drive towards the development of an effective vaccine and new chemotherapeutic targets for malaria, field-based studies on human malaria infection and laboratory-based studies using animal models of malaria offer complementary opportunities to further our understanding of the mechanisms behind malaria infection and pathology. We outline here the parallels between the Plasmodium chabaudi mouse model of malaria and human malaria. We will highlight the contribution of P. chabaudi to our understanding of malaria in particular, how the immune response in malaria infection is initiated and regulated, its role in pathology, and how immunological memory is maintained. We will also discuss areas where new tools have opened up potential areas of exploration using this invaluable model system.

Figure 1

Pathological features of P. chabaudi AS infection. The survival of mice aged 6–10 weeks infected intraperitoneally with 10⁵ P. chabaudi AS is dependent on mouse genetic background and differs between males (a) and females (b). Results are presented as the percentages of 5–15 mice per group surviving on a particular day; % circulating parasitemia (monitored by Giemsa-stained thin blood smears) peaks between days 7–9 and is higher in susceptible male mice [A/J and DBA/2 (c)] than in resistant male mice [B10.A and B10.D2 (d)]. Results are presented as the arithmetic means of 5–10 mice per group ± SEM. One surviving A/J male mouse which died at day 17 postinfection is represented with a broken line. During infection mice lose weight (e), become hypothermic (f) and hypoglycemic (g); all these parameters return to normal levels upon clearance of the peak of parasitemia. Data presented are the mean values ± SEM for five mice per group. Mice also become anemic from P. chabaudi infection (h). Resistant C57BL/6 (◆) and susceptible A/J (Δ) male mice were infected with 10⁶ P. chabaudi AS intraperitoneally and the number of circulating RBCs monitored for 18 d postinfection. Data represent means ± SEM for seven mice per group. The development of splenomegaly is shown in (i) (T. LeFevre, unpublished). Three naïve spleens are shown on the right, and three spleens from male C57BL/6 mice 20 d postinfection with 10⁵ P. chabaudi are shown on the left; the darker color in the latter indicates the accumulation of hemozoin, the insoluble parasite by-product. (a–g) modified from Cross and Langhorne [17] with permission. A/J males (■), B10.A males (◆), DBA/2 males (▲), B10.D2 males (▼), A/J females (□), DBA/2 females (△), B10.A females (◇) and B10.D2 females (▽). *, significantly different (P < 0.05); †, mortality. (h) reproduced from Chang et al. [24], with permission.