Dendritic cells devoid of IL-10 induce protective immunity against the protozoan parasite Trypanosoma cruzi.
In diverse models of microbial infections, protection is improved by immunization with dendritic cells (DC) loaded with whole pathogen lysate. However, pathogens that modulate DC function as a way to evade immunity may represent a challenge for these vaccination strategies. Thus, DC must be instructed in a particular manner to circumvent this issue and drive an effective immune response. Trypanosoma cruzi or its molecules alter DC function and, as we demonstrated, this phenomenon is associated with the parasite-driven stimulation of IL-10 production by DC. Here, we show that DC from IL-10-deficient mice pulsed in vitro with trypomastigote lysate secreted increased amounts of Th1-related cytokines and stimulated higher allogeneic and antigen-specific lymphocyte responses than their wild-type counterparts. In a model of DC-based immunization, these antigen-pulsed IL-10-deficient DC conferred protection against T. cruzi infection to recipient mice. Efficient immunity was associated with enhanced antigen-specific IFN-gamma production and endogenous DC activation. We illustrate for the first time a DC-based vaccination against T. cruzi and evidence the key role of IL-10 produced by sensitizing DC in inhibiting the induction of protection. These results support the rationale for vaccination strategies that timely suppress the effect of specific cytokines secreted by antigen presenting DC.
Alba Soto
Catalina D
CD
Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Argentina. catalina.alba@gmail.com
Solana
Maria Elisa
ME
Poncini
Carolina V
CV
Pino-Martinez
Agustina M
AM
Tekiel
Valeria
V
González-Cappa
Stella Maris
SM
D019264:Adoptive Transfer; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014349:Trypanosoma cruzi / Q000276:immunology
D000953:Antigens, Protozoan; D016753:Interleukin-10; D007371:Interferon-gamma