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Infection and Immunity, October 2005, p. 6552-6561, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6552-6561.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Transfection of Trypanosoma cruzi with Host CD40 Ligand Results in Improved Control of Parasite Infection

Mustapha Chamekh,1 Vincent Vercruysse,2 Mohammed Habib,2 Maxime Lorent,2 Michel Goldman,2 Abdelmounaïm Allaoui,1 and Bernard Vray2*

Laboratoire de Bactériologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium,1 Laboratoire d'Immunologie Expérimentale, Faculté de Médecine, and Laboratoire de Parasitologie, Département de Biologie des Organismes, Faculté des Sciences, Université Libre de Bruxelles, Brussels, Belgium2

Received 24 December 2005/ Returned for modification 9 March 2005/ Accepted 4 July 2005

We have previously shown that infection by Trypanosoma cruzi, a parasitic protozoan, is reduced by injection of CD40 ligand (CD40L)-transfected 3T3 fibroblasts (D. Chaussabel, F. Jacobs, J. de Jonge, M. de Veerman, Y. Carlier, K. Thielemans, M. Goldman, and B. Vray, Infect. Immun. 67:1929-1934, 1999). This prompted us to transfect T. cruzi with the murine CD40L gene and to study the consequences of this transfection on the course of infection. For this, epimastigotes (Y strain) were electroporated with the pTEX vector alone or the pTEX-CD40L construct, and transfected cells were selected for their resistance to Geneticin G418. Then strain Y-, pTEX-, and pTEX-CD40L-transfected epimastigotes were transformed by metacyclogenesis into mammalian infective forms called Y, YpTEX, and YpTEX-CD40L trypomastigotes. Transfection of the CD40L gene and expression of the CD40L protein were assessed by reverse transcription-PCR and Western blot analysis. The three strains of parasites were infective in vitro for mouse peritoneal macrophages. When organisms were inoculated into mice, a very low level of parasitemia and no mortality were seen with the YpTEX-CD40L strain compared to the Y and YpTEX strains. Furthermore, the proliferative capacity and the secretion of gamma interferon were both preserved in spleen cells (SCs) from YpTEX-CD40L-infected mice but not with SCs from Y- and YpTEX-infected mice. These results suggest that the CD40L produced by transfected T. cruzi is involved in the modulation of an antiparasite immune response. Moreover, mice surviving YpTEX-CD40L infection resisted a challenge infection with the wild-type strain. Taken together, our data demonstrate the feasibility of generating a T. cruzi strain expressing a bioactive host costimulatory molecule that counteracts the immunodeficiency induced by the parasite during infection and enhances protective immunity against a challenge infection.

* Corresponding author. Mailing address: Laboratoire d'Immunologie Expérimentale (CP 615), Faculté de Médecine, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium. Phone: 32 2 555 62 60. Fax: 32 2 555 63 60. E-mail: bvray{at}ulb.ac.be.

Editor: J. F. Urban, Jr.

Infection and Immunity, October 2005, p. 6552-6561, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6552-6561.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Habib, M., Rivas, M. N., Chamekh, M., Wieckowski, S., Sun, W., Bianco, A., Trouche, N., Chaloin, O., Dumortier, H., Goldman, M., Guichard, G., Fournel, S., Vray, B. (2007). Cutting Edge: Small Molecule CD40 Ligand Mimetics Promote Control of Parasitemia and Enhance T Cells Producing IFN-{gamma} during Experimental Trypanosoma cruzi Infection. J. Immunol. 178: 6700-6704 [Abstract] [Full Text]  
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