Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18,in Healthy BCG Vaccinated Adults

Tuberculosis remains an enormous global burden,despite wide vaccination coverage with the bacillus calmette-guérin (bcg),the only vaccine available against this disease,indicating that bcg-driven immunity is insufficient to protect the human population against tuberculosis. in this study we constructed recombinant bcg producing human il-18 (rbcghil-18) and investigated whether human il-18 produced by rbcghil-18 modulates dc functions and enhances th1 responses to mycobacterial antigens in humans. we found that the costimulatory cd86 and cd80 molecules were significantly upregulated on rbcghil-18-infected dcs,whereas the stimulation of dcs with nonrecombinant bcg was less effective. in contrast,both bcg strains decreased the dc-sign expression on human dcs. the rbcghil-18 increased il-23,il-10,and ip-10 production by dcs to a greater extent than nonrecombinant bcg. in a coculture system of cd4+ t cells and loaded dcs,rbcghil-18 favoured strong ifn-γ but also il-10 production by naive t cells but not by memory t cells. this was much less the case for nonrecombinant bcg. thus the expression of il-18 by recombinant bcg increases il-23,ip-10,and il-10 expression by human dcs and enhances their ability to induce ifn-γ and il-10 expression by naive t cells,without affecting the maturation phenotype of the dcs. © 2015 piotr szpakowski et al.