Dendritic cells devoid of IL-10 induce protective immunity against the protozoan

ALBA SOTO CATALINA D; SOLANA MARIA E; PONCINI CAROLINA V; PINO MARTINEZ AGUSTINA M.; TEKIEL VALERIA; GONZALEZ CAPPA STELLA M

VACCINE

ELSEVIER SCI LTD

Año: 2010 p. 7407 - 7413

0264-410X

In diverse models of microbial infections, protection is improved by immunization with dendritic cells (DC) loaded with whole pathogen lysate. However, pathogens that modulateDCfunction as awayto 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 alterDCfunction and, aswedemonstrated, thisphenomenonis associated with the parasitedriven 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 IFNgamma 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