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Infection and Immunity, August 2005, p. 4777-4786, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4777-4786.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Species-Specific Inhibition of Cerebral Malaria in Mice Coinfected with Plasmodium spp.

Tatiana Voza,1 Ana M. Vigário,2 Elodie Belnoue,2 Anne Charlotte Grüner,2 Jean-Christophe Deschemin,2 Michèle Kayibanda,2 Florian Delmas,1 Chris J. Janse,3 Blandine Franke-Fayard,3 Andrew P. Waters,3 Irène Landau,1,{dagger} Georges Snounou,1,4,{dagger}* and Laurent Rénia2,{dagger}

Equipe Parasitologie Comparée et Modèles Expérimentaux USM 307, CNRS IFR 101, Laboratoire de Protozoologie et Parasitologie Comparée, EPHE, Muséum National d'Histoire Naturelle, CP52, 61 Rue Buffon, 75231 Paris Cedex 05, France,1 Département d'Immunologie, INSERM U567, CNRS UMR 8104, Université René Descartes, Hôpital Cochin, 75014 Paris, France,2 Department of Parasitology, Malaria Group, Leiden University Medical Center, Leiden, The Netherlands,3 Unité de Parasitologie Biomédicale, CNRS URA 2581, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris Cedex 15, France4

Received 4 November 2004/ Returned for modification 8 January 2005/ Accepted 10 March 2005

Recent epidemiological observations suggest that clinical evolution of Plasmodium falciparum infections might be influenced by the concurrent presence of another Plasmodium species, and such mixed-species infections are now known to occur frequently in residents of most areas of endemicity. We used mice infected with P. berghei ANKA (PbA), a model for cerebral malaria (CM), to investigate the influence of experimental mixed-species infections on the expression of this pathology. Remarkably, the development of CM was completely inhibited by the simultaneous presence of P. yoelii yoelii but not that of P. vinckei or another line of P. berghei. In the protected coinfected mice, the accumulation of CD8+ T cells in the brain vasculature, a pivotal step in CM pathogenesis, was found to be abolished. Protection from CM was further found to be associated with species-specific suppression of PbA multiplication. These observations establish the concept of mixed Plasmodium species infections as potential modulators of pathology and open novel avenues to investigate mechanisms implicated in the pathogenesis of malaria.

* Corresponding author. Mailing address: Muséum National d'Histoire Naturelle, Equipe Parasitologie Comparée et Modèles Expérimentaux USM 307, CNRS IFR 101, CP52, 61 Rue Buffon, 75231 Paris Cedex 05, France. Phone: 33-1-40-79-34-98. Fax: 33-1-40-79-34-99. E-mail: snounou{at}mnhn.fr.

Editor: J. F. Urban, Jr.

{dagger} I.L., G.S., and L.R. contributed equally to this study.

Infection and Immunity, August 2005, p. 4777-4786, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4777-4786.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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