IFN- improves BCG immunogenicity by acting on DC maturation

Abstract: Given the variable protective efficacy provided by Mycobacterium bovis bacillus Calmette-Guérin (BCG), there is an urgent need to develop new vaccines against tuberculosis. As dendritic cells (DC) play a critical role in initiating and reg-ulating a protective T cell response against the pathogens, the comprehension of mycobacterium-induced modulation of DC functions is critical to pinpoint new, immunological strategies. To this end, a comparative analysis of the effect induced by BCG and Mycobacterium tuberculosis (Mtb) in-fection on the DC immunophenotype indicated that BCG is less efficient in inducing DC maturation than Mtb. In addition, BCG-infected DC poorly expressed IFN- and displayed a reduced produc-tion of IL-12 as compared with Mtb-stimulated cells. The impaired expression of IL-12p35 and IFN- is likely a result of the inability of BCG to induce the activation of the IFN regulatory fac-tor-3. Taking into account these data, we sought to investigate whether the exogenous addition of IFN-, a cytokine that exerts important effects on the immune system, could enhance the Th1-polar-izing capacity of BCG-infected DC. Interestingly, when DC infected by BCG were pretreated in vitro with IFN-, they displayed a fully mature pheno-type and released a significant amount of bioactive IL-12p70, which resulted in an enhanced Th1 re-sponse. This study demonstrates that IFN- poten-tiates DC immunological functions following BCG infection, thus suggesting IFN- as a possibile can-didate as vaccine adjuvant. J. Leukoc. Biol. 85