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Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity

Genes & Immunity volume 6, pages 416–421 (2005)Cite this article

Abstract

Unprecedented cure after infection with the lethal Plasmodium berghei ANKA was observed in an F2 progeny generated by intercrossing the wild-derived WLA and the laboratory C57BL/6 mouse strains. Resistant mice were able to clear parasitaemia and establish immunity. The observed resistance was disclosed as a combinatorial effect of genetic factors derived from the two parental strains. Genetic mapping of survival time showed that the WLA allele at a locus on chromosome 1 (colocalizing with Berghei resistance 1 (Berr1), a locus associated with resistance to experimental cerebral malaria) increases the probability to resist early death. Also, the C57Bl/6 allele at a novel locus on chromosome 9 (Berr3) confers overall resistance to this lethal Plasmodium infection. This report underlines the value of using wild-derived mouse strains to identify novel genetic factors in the aetiology of disease phenotypes, and provides a unique model for studying parasite clearance and immunity associated with malaria.

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Acknowledgements

We are very grateful to Isabelle Lanctin and Danièle Voegtlé for technical assistance. We are most indebted to António Coutinho, Maria Mota, Sarah Auburn and Taane Clark for continuous support during the development of this work and for critical reading of the manuscript. This work was supported by the Fundação para a Ciência e Tecnologia, Portugal (36392/99), and by the CNRS LEA ‘Génétique et dévelopement de la tolérance naturelle’. It was also supported by the Fundação Calouste Gulbenkian, ICCTI, French Embassy in Lisbon, by the ‘Programme de recherche fondamentale en microbiologie, maladies infectieuses et parasitaires’ of the French Ministry of Research, by INSERM U511 and by the Swedish Research Council.

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Author notes

  1. S Campino and S Bagot: Both these authors contributed equally to this work.

Authors and Affiliations

  1. Instituto Gulbenkian de Ciência, Oeiras, Portugal

    S Campino, M-L Bergman, P Almeida, N Sepúlveda, S Pied, C Penha-Gonçalves & D Holmberg

  2. Medical and Clinical Genetics, Umeå University, Umeå, Sweden

    S Campino, M-L Bergman & D Holmberg

  3. Département d'Immunologie, Unité d'Immunophysiopathologie Infectieuse, Institut Pasteur, Paris, France

    S Bagot, S Pied & P-A Cazenave

Authors
  1. S Campino
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  2. S Bagot
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  3. M-L Bergman
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  4. P Almeida
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  5. N Sepúlveda
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  6. S Pied
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  7. C Penha-Gonçalves
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  8. D Holmberg
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  9. P-A Cazenave
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Corresponding author

Correspondence to P-A Cazenave.

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Campino, S., Bagot, S., Bergman, ML. et al. Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity. Genes Immun 6, 416–421 (2005). https://doi.org/10.1038/sj.gene.6364219

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  • DOI: https://doi.org/10.1038/sj.gene.6364219

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