Trends in Parasitology
Volume 28, Issue 2, February 2012, Pages 73-82
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Review
The contribution of Plasmodium chabaudi to our understanding of malaria

https://doi.org/10.1016/j.pt.2011.10.006Get rights and content

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.

Section snippets

The rodent malarias: from the gallery forest to the lab

In the years following the discovery by Vincke in 1948 that malaria parasites infect African rodents, these parasites (Box 1) have been used extensively in laboratory research on malaria. Their use has informed almost every subdiscipline of malariology, including parasite genetics, genomics, immunology, evolutionary biology, and ecological studies. It is not our intent to cover all of these areas, but instead to discuss some of the most fruitful areas to date and highlight some of the crucial

P. chabaudi displays striking hematological similarities to P. falciparum

Different Plasmodium spp invade erythrocytes at particular stages in red blood cell (RBC) development; the availability of the preferred RBC type determines much of the dynamics of infection. P. falciparum invades RBCs of all ages, whereas P. vivax displays a preference for immature RBCs (reticulocytes). The preferences for the rodent parasites are detailed in Table 1, but it is notable that, as with P. falciparum, P. chabaudi invades both normocytes and reticulocytes [9]; however, unlike the

P. chabaudi can be used to dissect mechanisms of pathology in malaria infection

Mice infected with P. chabaudi display an array of symptoms which start late in the peak of infection and resolve as the parasite is cleared (Figure 1, Table 2) [17]. The pathogenesis of malaria infection in humans is multi-factorial, but may be considered to centre around three interlinked phenomena: (i) immune response-induced severe malarial anemia (SMA) [18], (ii) sequestration of iRBCs to activated endothelial cells [14], and (iii) metabolic acidosis, one of the strongest predictors of

Host genetics influences the severity of malaria in both humans and mice

In endemic areas, malaria represents a spectrum of disease as a result of the complex interplay between environmental factors (such as transmission intensity) and host and parasite genetics. At least one large genetic study is currently ongoing in humans, but the influence of host genetics on malaria severity can be seen in studies using the P. chabaudi mouse model of malaria. Infection with P. chabaudi (clone AS) leads to a peak parasitemia of 20–50% of iRBCs between days seven and ten

Unraveling parasite genetics using the P. chabaudi mouse model

Parasite genetics are also a major determinant in the pathogenesis of malaria infection. P. falciparum as a species consists of many different strains, some of which have been shown to differ in characteristics such as rosetting, which shows a positive correlation with the severity of malaria [32]. Although P. chabaudi clone AS is normally the first choice of clone for laboratory researchers working with the P. chabaudi mouse model of malaria (it is the best-characterized P. chabaudi clone),

Immune mechanisms

Due to similarities with the human immune response to Plasmodium infections summarized in Table 3, the immunology of P. chabaudi blood-stage infections has been well-studied. Study of the initiation and regulation of the immune response, and immunological memory to P. chabaudi, have contributed useful hypotheses for further study in human malaria that are highlighted here as examples of what can be achieved.

Concluding remarks

Owing to the extensive similarities between P. chabaudi-infected mice and human infection with Plasmodium spp, as well as the spectrum of models available from different combinations of mouse and parasite variants, P. chabaudi offers an unrivalled system for laboratory investigations of malaria. Recent advances in genetic manipulation of P. chabaudi, specifically the ability to perform transfection [104], offer multiple opportunities, as suggested in Box 2, including for the study of

Acknowledgments

The authors would like to thank Julie Gutman for insightful discussion and Alberto Moreno and Richard Carter for critical reading of the manuscript. The authors apologize to those authors whose work could not be cited due to space constraints.

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