Toxoplasma gondii antigen-pulsed-dendritic cell-derived exosomes induce a protective immune response against T. gondii infection.
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.
Aline
Fleur
F
UFR des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 Tours, France.
Bout
Daniel
D
Amigorena
Sébastian
S
Roingeard
Philippe
P
Dimier-Poisson
Isabelle
I
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology*; D000954:Antigens, Surface / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D000941:Antigens; D000954:Antigens, Surface; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M