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Infection and Immunity, June 2005, p. 3531-3539, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3531-3539.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Impairment of Protective Immunity to Blood-Stage Malaria by Concurrent Nematode Infection

McGill Centre for the Study of Host Resistance, Research Institute of McGill University Health Centre,¹ McGill Centre for Host-Parasite Interactions, Institute of Parasitology, McGill University, Ste Anne de Bellevue, Quebec, Canada,² Departments of Human Genetics and Medicine, McGill University, Montreal³

Received 12 October 2004/ Returned for modification 19 November 2004/ Accepted 2 February 2005

Helminthiases, which are highly prevalent in areas where malaria is endemic, have been shown to modulate or suppress the immune response to unrelated antigens or pathogens. In this study, we established a murine model of coinfection with a gastrointestinal nematode parasite, Heligmosomoides polygyrus, and the blood-stage malaria parasite Plasmodium chabaudi AS in order to investigate the modulation of antimalarial immunity by concurrent nematode infection. Chronic infection with the nematode for 2, 3, or 5 weeks before P. chabaudi AS infection severely impaired the ability of C57BL/6 mice to control malaria, as demonstrated by severe mortality and significantly increased malaria peak parasitemia levels. Coinfected mice produced significantly lower levels of gamma interferon (IFN-) during P. chabaudi AS infection than mice infected with malaria alone. Concurrent nematode infection also suppressed production of type 1-associated, malaria-specific immunoglobulin G2a. Mice either infected with the nematode alone or coinfected with the nematode and malaria had high transforming growth factor ß1 (TGF-ß1) levels, and concurrent nematode and malaria infections resulted in high levels of interleukin-10 in vivo. Splenic CD11c⁺ dendritic cells (DC) from mice infected with malaria alone and coinfected mice showed similarly increased expression of CD40, CD80, and CD86, but DC from coinfected mice were unable to induce CD4⁺ T-cell proliferation and optimal IFN- production in response to the malaria antigen in vitro. Importantly, treatment of nematode-infected mice with an anthelmintic drug prior to malaria infection fully restored protective antimalarial immunity and reduced TGF-ß1 levels. These results demonstrate that concurrent nematode infection strongly modulates multiple aspects of immunity to blood-stage malaria and consequently impairs the development of protective antimalarial immunity.

Editor: J. F. Urban, Jr.

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