Antibody Recognition of Rodent Malaria Parasite Antigens Exposed at the Infected Erythrocyte Surface: Specificity of Immunity Generated in Hyperimmune Mice

ABSTRACT In regions where malaria is endemic, inhabitants remain susceptible to repeated reinfection as they develop and maintain clinical immunity. This immunity includes responses to surface-exposed antigens onPlasmodium sp.-infected erythrocytes. Some of these parasite-encoded antigens may be diverse and phenotypically variable, and the ability to respond to this diversity and variability is an important component of acquired immunity. Characterizing the relative specificities of antibody responses during the acquisition of immunity and in hyperimmune individuals is thus an important adjunct to vaccine research. This is logistically difficult to do in the field but is relatively easily carried out in animal models. Infections in inbred mice with rodent malaria parasite Plasmodium chabaudi chabaudi AS represent a good model for Plasmodium falciparum in humans. This model has been used in the present study in a comparative analysis of cross-reactive and specific immune responses in rodent malaria. CBA/Ca mice were rendered hyperimmune toP. chabaudi chabaudi (AS or CB lines) or Plasmodium berghei (KSP-11 line) by repeated infection with homologous parasites. Serum from P. chabaudi chabaudi AS hyperimmune mice reacted with antigens released from disrupted P. chabaudi chabaudi AS-infected erythrocytes, but P. chabaudi chabaudi CB and P. berghei KSP-11 hyperimmune serum also contained cross-reactive antibodies to these antigens. However, antibody activity directed against antigens exposed at the surfaces of intact P. chabaudi chabaudi-infected erythrocytes was mainly parasite species specific and, to a lesser extent, parasite line specific. Importantly, this response included opsonizing antibodies, which bound to infected erythrocytes, leading to their phagocytosis and destruction by macrophages. The results are discussed in the context of the role that antibodies to both variable and invariant antigens may play in protective immunity in the face of continuous susceptibility to reinfection.

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A cornucopia of research resources for the fourth rodent malaria parasite species

BMC Biology ◽

10.1186/s12915-021-01019-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jane M. Carlton

Keyword(s):

Malaria Parasite ◽

Parasite Species ◽

First Century ◽

Model Systems ◽

Rodent Malaria Parasite ◽

Malaria Parasites ◽

Rodent Malaria ◽

Human Malaria ◽

Plasmodium Vinckei ◽

Research Resources

AbstractThe study of human malaria caused by species of Plasmodium has undoubtedly been enriched by the use of model systems, such as the rodent malaria parasites originally isolated from African thicket rats. A significant gap in the arsenal of resources of the species that make up the rodent malaria parasites has been the lack of any such tools for the fourth of the species, Plasmodium vinckei. This has recently been rectified by Abhinay Ramaprasad and colleagues, whose pivotal paper published in BMC Biology describes a cornucopia of new P. vinckei ‘omics datasets, mosquito transmission experiments, transfection protocols, and virulence phenotypes, to propel this species firmly into the twenty-first century.

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Expression profiles of peroxiredoxin proteins of the rodent malaria parasite Plasmodium yoelii

International Journal for Parasitology ◽

10.1016/s0020-7519(03)00184-x ◽

2003 ◽

Vol 33 (13) ◽

pp. 1455-1461 ◽

Cited By ~ 20

Author(s):

Shin-ichiro Kawazu ◽

Tomoyoshi Nozaki ◽

Takafumi Tsuboi ◽

Yoko Nakano ◽

Kanako Komaki-Yasuda ◽

...

Keyword(s):

Malaria Parasite ◽

Expression Profiles ◽

Plasmodium Yoelii ◽

Rodent Malaria Parasite ◽

Rodent Malaria ◽

Parasite Plasmodium

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Acute Plasmodium chabaudi chabaudi Malaria Infection Induces Antibodies Which Bind to the Surfaces of Parasitized Erythrocytes and Promote Their Phagocytosis by Macrophages In Vitro

Infection and Immunity ◽

10.1128/iai.66.9.4080-4086.1998 ◽

1998 ◽

Vol 66 (9) ◽

pp. 4080-4086 ◽

Cited By ~ 52

Author(s):

Maria M. Mota ◽

K. Neil Brown ◽

Anthony A. Holder ◽

William Jarra

Keyword(s):

Parasite Clearance ◽

Enzyme Linked Immunosorbent Assay ◽

Antibody Activity ◽

Parasite Line ◽

Primary Role ◽

Plasmodium Chabaudi ◽

Species Specific ◽

Cellular Immune ◽

Variant Line

ABSTRACT CBA/Ca mice infected with 5 × 104 Plasmodium chabaudi chabaudi AS-parasitized erythrocytes experience acute but self-limiting infections of relatively short duration. Parasitemia peaks (∼40% infected erythrocytes) on day 10 or 11 and is then partially resolved over the ensuing 5 to 6 days, a period referred to as crisis. How humoral and cellular immune mechanisms contribute to parasite killing and/or clearance during crisis is controversial. Humoral immunity might be parasite variant, line, or species specific, while cellular immune responses would be relatively less specific. For P. c. chabaudi AS, parasite clearance is largely species and line specific during this time, which suggests a primary role for antibody activity. Accordingly, acute-phase plasma (APP; taken fromP. c. chabaudi AS-infected mice at day 11 or 12 postinfection) was examined for the presence of parasite-specific antibody activity by enzyme-linked immunosorbent assay. Antibody binding to the surface of intact, live parasitized erythrocytes, particularly those containing mature (trophozoite and schizont) parasites, was demonstrated by immunofluorescence in APP and the immunoglobulin G (IgG)-containing fraction thereof. Unfractionated APP (from P. c. chabaudi AS-infected mice), as well as its IgG fraction, specifically mediated the opsonization and internalization of P. c. chabaudi AS-parasitized erythrocytes by macrophages in vitro. APP from another parasite line (P. c. chabaudi CB) did not mediate the same effect against P. c. chabaudi AS-parasitized erythrocytes. These results, which may represent one mechanism of parasite removal during crisis, are discussed in relation to the parasite variant, line, and species specificity of parasite clearance during this time.

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Improved transfection and new selectable markers for the rodent malaria parasite Plasmodium yoelii

Molecular and Biochemical Parasitology ◽

10.1016/j.molbiopara.2006.01.001 ◽

2006 ◽

Vol 146 (2) ◽

pp. 242-250 ◽

Cited By ~ 47

Author(s):

Artemio M. Jongco ◽

Li-Min Ting ◽

Vandana Thathy ◽

Maria M. Mota ◽

Kami Kim

Keyword(s):

Malaria Parasite ◽

Plasmodium Yoelii ◽

Rodent Malaria Parasite ◽

Selectable Markers ◽

Rodent Malaria ◽

Parasite Plasmodium

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Malaria Parasites Can Develop Stable Resistance to Artemisinin but Lack Mutations in Candidate Genes atp6 (Encoding the Sarcoplasmic and Endoplasmic Reticulum Ca2+ ATPase), tctp, mdr1, and cg10

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.50.2.480-489.2006 ◽

2006 ◽

Vol 50 (2) ◽

pp. 480-489 ◽

Cited By ~ 137

Author(s):

A. Afonso ◽

P. Hunt ◽

S. Cheesman ◽

A. C. Alves ◽

C. V. Cunha ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Plasmodium Falciparum ◽

Copy Number ◽

Malaria Parasite ◽

Field Studies ◽

Rodent Malaria Parasite ◽

Malaria Parasites ◽

Rodent Malaria ◽

First Time ◽

Genetic Modulators

ABSTRACT Resistance of Plasmodium falciparum to drugs such as chloroquine and sulfadoxine-pyrimethamine is a major problem in malaria control. Artemisinin (ART) derivatives, particularly in combination with other drugs, are thus increasingly used to treat malaria, reducing the probability that parasites resistant to the components will emerge. Although stable resistance to artemisinin has yet to be reported from laboratory or field studies, its emergence would be disastrous because of the lack of alternative treatments. Here, we report for the first time, to our knowledge, genetically stable and transmissible ART and artesunate (ATN)-resistant malaria parasites. Each of two lines of the rodent malaria parasite Plosmodium chabaudi chabaudi, grown in the presence of increasing concentrations of ART or ATN, showed 15-fold and 6-fold increased resistance to ART and ATN, respectively. Resistance remained stable after cloning, freeze-thawing, after passage in the absence of drug, and transmission through mosquitoes. The nucleotide sequences of the possible genetic modulators of ART resistance (mdr1, cg10, tctp, and atp6) of sensitive and resistant parasites were compared. No mutations in these genes were identified. In addition we investigated whether changes in the copy number of these genes could account for resistance but found that resistant parasites retained the same number of copies as their sensitive progenitors. We believe that this is the first report of a malaria parasite with genetically stable and transmissible resistance to artemisinin or its derivatives.

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