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Infection and Immunity, July 2004, p. 4127-4137, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.4127-4137.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Toxoplasma gondii Antigen-Pulsed-Dendritic Cell-Derived Exosomes Induce a Protective Immune Response against T. gondii Infection

Fleur Aline,1 Daniel Bout,1 Sébastian Amigorena,2 Philippe Roingeard,3 and Isabelle Dimier-Poisson1*

UMR Université-INRA d'Immunologie Parasitaire et Vaccinologie, UFR des Sciences Pharmaceutiques, IFR Imagerie et Exploration Fonctionnelles, 37200 Tours,1 INSERM U520, Institut Curie, 75005 Paris,2 Laboratoires de Biologie Cellulaire et Virologie, EA 2639, Analyse Structurale des Antigènes, IFR Transposons et Virus, Faculté de Médecine, 37032 Tours Cedex, France3

Received 14 January 2004/ Returned for modification 16 February 2004/ Accepted 9 March 2004

It was previously demonstrated that immunizing mice with spleen dendritic cells (DCs) that had been pulsed ex vivo with Toxoplasma gondii antigens triggers a systemic Th1-biased specific immune response and induces protection against infection. T. gondii can cause severe sequelae in the fetuses of mothers who acquire the infection during pregnancy, as well as life-threatening neuropathy in immunocompromised patients, in particular those with AIDS. Here, we investigate the efficacy of a novel cell-free vaccine composed of DC exosomes, which are secreted antigen-presenting vesicles that express functional major histocompatibility complex class I and II and T-cell-costimulatory molecules. They have already been shown to induce potent antitumor immune responses. We investigated the potential of DC2.4 cell line-derived exosomes to induce protective immunity against toxoplasmosis. Our data show that most adoptively transferred T. gondii-pulsed DC-derived exosomes were transferred to the spleen, elicited a strong systemic Th1-modulated Toxoplasma-specific immune response in vivo, and conferred good protection against infection. These findings support the possibility that DC-derived exosomes can be used for T. gondii immunoprophylaxis and for immunoprophylaxis against many other pathogens.

* Corresponding author. Mailing address: UFR des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 Tours, France. Phone: 33-2-47-36-71-85. Fax: 33-2-47-36-72-52. E-mail: dimier{at}univ-tours.fr.

Editor: W. A. Petri, Jr.

Infection and Immunity, July 2004, p. 4127-4137, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.4127-4137.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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