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Infection and Immunity, August 2003, p. 4375-4381, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4375-4381.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Transfected Plasmodium knowlesi Produces Bioactive Host Gamma Interferon: a New Perspective for Modulating Immune Responses to Malaria Parasites

Hastings Ozwara,1,2 Jan A. M. Langermans,1 Clemens H. M. Kocken,1 Annemarie van der Wel,1 Peter H. van der Meide,3 Richard A. W. Vervenne,1 Jason M. Mwenda,2 and Alan W. Thomas1*

Biomedical Primate Research Centre, Department of Parasitology, 2280 GH Rijswijk,1 U-Cytech bv, Utrecht University, 3584 CJ Utrecht The Netherlands,3 Institute of Primate Research, National Museums of Kenya, Karen, Nairobi, Kenya2

Received 14 August 2002/ Returned for modification 14 November 2002/ Accepted 19 May 2003

Transgenic pathogenic microorganisms expressing host cytokines such as gamma interferon (IFN-{gamma}) have been shown to manipulate host-pathogen interaction, leading to immunomodulation and enhanced protection. Expression of host cytokines in malaria parasites offers the opportunity to investigate the potential of an immunomodulatory approach by generating immunopotentiated parasites. Using the primate malaria parasite Plasmodium knowlesi, we explored the conditions for expressing host cytokines in malaria parasites. P. knowlesi parasites transfected with DNA constructs for expressing rhesus monkey (Macaca mulatta) IFN-{gamma} under the control of the heterologous P. berghei apical membrane antigen 1 promoter, produced bioactive IFN-{gamma} in a developmentally regulated manner. IFN-{gamma} expression had no marked effect on in vitro parasite development. Bioactivity of the parasite-produced IFN-{gamma} was shown through inhibition of virus cytopathic effect and confirmed by using M. mulatta peripheral blood cells in vitro. These data indicate for the first time that it is feasible to generate malaria parasites expressing bioactive host immunomodulatory cytokines. Furthermore, cytokine-expressing malaria parasites offer the opportunity to analyze cytokine-mediated modulation of malaria during the blood and liver stages of the infection.

* Corresponding author. Mailing address: Biomedical Primate Research Centre, Department of Parasitology, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands. Phone: 31 15 2842538. Fax: 31 15 2843986. E-mail: thomas{at}bprc.nl.

Editor: J. M. Mansfield

Infection and Immunity, August 2003, p. 4375-4381, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4375-4381.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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