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Infection and Immunity, May 2009, p. 1827-1834, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01321-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Variant-Specific Immunity to Plasmodium berghei in Pregnant Mice {triangledown}

Rosette Megnekou,1,2,3 Lars Hviid,1,2* and Trine Staalsoe1,2

Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen,1 Centre for Medical Parasitology, Department of Clinical Microbiology and Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark,2 Biotechnology Centre and Faculty of Science, University of Yaounde I, Yaounde, Cameroon3

Received 30 October 2008/ Returned for modification 4 December 2008/ Accepted 17 February 2009

We have investigated the immunological basis of pregnancy-related Plasmodium berghei recrudescence in immune mice with substantial preexisting immunity. Specifically, we examined the relevance of this experimental model to the study of pregnancy-associated malaria (PAM) caused by P. falciparum in women with substantial preexisting protective immunity. We used mice with immunity induced prior to pregnancy and employed flow cytometry to assess their levels of immunoglobulin G (IgG) recognizing antigens on the surfaces of infected erythrocytes (IEs) in plasma. After immunization, the mice did not possess IgG specific for antigens on IEs obtained during pregnancy-related recrudescence but they acquired recrudescence-specific IgG over the course of several pregnancies and recrudescences. In contrast, levels of antibodies recognizing IEs from nonpregnant mice did not increase with increasing parity. Furthermore, maternal hemoglobin levels increased and pregnancy-related parasitemia decreased with increasing parity. Finally, parasitemic mice produced smaller litters and pups with lower weights than nonparasitemic mice. Taken together, these observations suggest that levels of antibodies specific for recrudescence-type IEs are related to the protection of pregnant mice from maternal anemia, low birth weight, and decreased litter size. We conclude that the model replicates many of the key parasitological and immunological features of PAM, although the P. berghei genome does not encode proteins homologous to the P. falciparum erythrocyte membrane protein 1 adhesins, which are of key importance in P. falciparum malaria. The study of P. berghei malaria in pregnant, immune mice can be used to gain significant new insights regarding malaria pathogenesis and immunity in general and regarding PAM in particular.


* Corresponding author. Mailing address: Department of International Health, Immunology and Microbiology, University of Copenhagen, CSS Building 22, Øster Farimagsgade 5, 1014 Copenhagen K, Denmark. Phone: 45 3545 6099. Fax: 45 3532 7851. E-mail: lhcmp{at}rh.dk

{triangledown} Published ahead of print on 23 February 2009.

Editor: J. F. Urban, Jr.


Infection and Immunity, May 2009, p. 1827-1834, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01321-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.