Plasmodium chabaudi: Antigenic variation during recrudescent parasitaemias in mice

McLean, Sheila A.M.; Pearson, C.; Phillips, R. S.

doi:10.1016/0014-4894(82)90038-8

Cited by 93 publications

(54 citation statements)

References 10 publications

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“…As in previous studies (McLean et al 1982;Jarra & Brown 1985;Jarra et al 1986;Bates et al 1988), we found evidence of strain-speci¢c immunity directed against asexual parasites (¢gure 2a). Immunization also reduced gametocyte densities, but there was no evidence that this reduction had a strain-speci¢c component (¢gure 2b).…”

Section: Discussionsupporting

confidence: 89%

The effect of partial host immunity on the transmission of malaria parasites

Buckling

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2001

Proc. R. Soc. Lond. B

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Experiments were carried out to determine the e¡ect of partial host immunity against the rodent malaria parasite Plasmodium chabaudi on the transmission success of the parasite. There was a fourfold reduction in both the blood-stage, asexually replicating parasite density and the gametocyte (transmissable stage) density in immunized hosts. Some of the reduction in asexual parasite densities was due to strain-speci¢c immunity, but there was no evidence that strain-speci¢c immunity a¡ected gametocyte densities. However, immunity did a¡ect transmission in a strain-speci¢c manner, with a ¢vefold reduction in gametocyte infectivity to mosquitoes in homologous challenges compared with heterologous challenges or non-immunized controls. This implies the existence of a mechanism of strain-speci¢c infectivity-reducing immunity that does not a¡ect the density of gametocytes circulating in peripheral blood. The proportion of asexual parasites that produced gametocytes increased during the course of infection in both non-immunized and in immunized hosts, but immunity increased gametocyte production early in the infection.

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Section: Discussionsupporting

confidence: 89%

The effect of partial host immunity on the transmission of malaria parasites

Buckling

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2001

Proc. R. Soc. Lond. B

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“…Like cytoadherence, perhaps the most compelling evidence that antigenic variation confers a fitness advantage is its prevalence throughout the Plasmodium genus. Evidence for antigenic variation exists in all species of parasite studied (P. berghei (Cox 1962); P. knowlesi (Brown & Brown 1965); P. cynomolgi (Voller & Rossan 1969); P. falciparum Biggs et al 1991;Roberts et al 1992); P. chabaudi (McLean et al 1982); P. fragile (Handunetti et al 1987); and probably P. vivax del Portillo et al 2001)). Different sets of genes are responsible in different species (Howard & Barnwell 1985;al-Khedery et al 1999;del Portillo et al 2001;Janssen et al 2001Janssen et al , 2002, suggesting convergent evolution for this phenotype.…”

Section: (B) Antigenic Variationmentioning

confidence: 99%

Virulence in malaria: an evolutionary viewpoint

Mackinnon

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2004

Phil. Trans. R. Soc. Lond. B

227

205

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Malaria parasites cause much morbidity and mortality to their human hosts. From our evolutionary perspective, this is because virulence is positively associated with parasite transmission rate. Natural selection therefore drives virulence upwards, but only to the point where the cost to transmission caused by host death begins to outweigh the transmission benefits. In this review, we summarize data from the laboratory rodent malaria model, Plasmodium chabaudi, and field data on the human malaria parasite, P. falciparum, in relation to this virulence trade-off hypothesis. The data from both species show strong positive correlations between asexual multiplication, transmission rate, infection length, morbidity and mortality, and therefore support the underlying assumptions of the hypothesis. Moreover, the P. falciparum data show that expected total lifetime transmission of the parasite is maximized in young children in whom the fitness cost of host mortality balances the fitness benefits of higher transmission rates and slower clearance rates, thus exhibiting the hypothesized virulence trade-off. This evolutionary explanation of virulence appears to accord well with the clinical and molecular explanations of pathogenesis that involve cytoadherence, red cell invasion and immune evasion, although direct evidence of the fitness advantages of these mechanisms is scarce. One implication of this evolutionary view of virulence is that parasite populations are expected to evolve new levels of virulence in response to medical interventions such as vaccines and drugs.

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“…Peak parasitemias were significantly higher in subpa- tently infected mice than in patently infected mice challenged with CB parasites (P Ͻ 0.01). Previous studies have shown that during P. c. chabaudi AS infection, recrudescent parasites express different variant surface antigens from those expressed by parasites that dominate the primary peak (25,26,30). To compare immunity to parasites expressing homologous and heterologous variant surface antigens, parasites were collected during the primary peak ("primary variant") or recrudescent peak ("recrudescent variant") of a P. c. chabaudi AS infection in a single mouse and frozen in multiple aliquots.…”

Section: Specificity Of Immunity Induced By Subpatent Infectionmentioning

confidence: 99%

Heterologous Immunity in the Absence of Variant-Specific Antibodies after Exposure to Subpatent Infection with Blood-Stage Malaria

2005

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We examined immunity induced by subpatent blood-stage malaria (undetectable by microscopy) using the rodent malaria parasite, Plasmodium chabaudi chabaudi, postulating that limited infection may allow expansion of antigen-specific T cells that are normally deleted by apoptosis. After three infections drug cured at 48 h, mice were protected against high-dose challenge with homologous or heterologous parasites (different strain or variant). Immunity differed from that generated by three untreated, patent infections. Subpatently infected mice lacked immunoglobulin G (IgG) to variant surface antigens, despite producing similar titers of total malaria-specific IgG to those produced by patently infected mice, including antibodies specific for merozoite surface antigens conserved between heterologous strains. Antigen-specific proliferation of splenocytes harvested prechallenge was significantly higher in subpatently infected mice than in patently infected or naive mice. In subpatently infected mice, lymphoproliferation was similar in response to homologous and heterologous parasites, suggesting that antigenic targets of cell-mediated immunity were conserved. A Th1 cytokine response was evident during challenge. Apoptosis of CD4؉ and CD8 ؉ splenic lymphocytes occurred during patent but not subpatent infection, suggesting a reason for the relative prominence of cell-mediated immunity after subpatent infection. In conclusion, subpatent infection with blood stage malaria parasites induced protective immunity, which differed from that induced by patent infection and targeted conserved antigens. These findings suggest that alternative vaccine strategies based on delivery of multiple parasite antigens at low dose may induce effective immunity targeting conserved determinants.In regions where Plasmodium falciparum malaria transmission is high, individuals eventually acquire nonsterile immunity, where low parasitemia may occur in the absence of clinical symptoms. Immunity to blood-stage malaria appears to be predominantly antibody mediated. Transfusion of gamma globulin from immune adults to children with severe malaria is associated with reduced parasitemia and clinical improvement (5). Merozoite surface antigens (2, 6, 32) and variant antigens expressed on the surface of malaria-infected erythrocytes (including PfEMP1) (3, 23) are both targets of protective antibody responses.It is still unclear whether cell-mediated (antibody-independent) immune responses play a major role in naturally acquired immunity to blood-stage malaria in humans (reviewed in reference 9). Loss or suppression of malaria-specific T cells during the course of natural infection may limit the contribution of inflammatory T cells to protective immunity. Reduced numbers of peripheral blood T lymphocytes and diminished proliferative responses to in vitro stimulation with malarial antigens are observed during acute P. falciparum infection (15-17). Animal studies indicate that malaria-specific effector and helper CD4 ϩ T cells are deleted by apoptosis during in...

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Plasmodium chabaudi: Antigenic variation during recrudescent parasitaemias in mice

Cited by 93 publications

References 10 publications

The effect of partial host immunity on the transmission of malaria parasites

The effect of partial host immunity on the transmission of malaria parasites

Virulence in malaria: an evolutionary viewpoint

Heterologous Immunity in the Absence of Variant-Specific Antibodies after Exposure to Subpatent Infection with Blood-Stage Malaria

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