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

Piotr Szpakowski (1) , Franck Biet (2) , Camille Locht (3) , Małgorzata Paszkiewicz (1) , Wieslawa Rudnicka (1) , Fabrice Allain (4) , Marek Fol (1) , Joel Pestel (4) , Magdalena Kowalewicz-Kulbat (1)

1 Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology
2 UMR ISP - Infectiologie et Santé Publique
3 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
4 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576

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.

Domaines: Microbiologie et Parasitologie

Piotr Szpakowski, Franck Biet, Camille Locht, Małgorzata Paszkiewicz, Wieslawa Rudnicka, et al.. Dendritic Cell Activity Driven by Recombinant [i]Mycobacterium bovis[/i] BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults. Journal of Immunology Research, 2015, pp.1-13. ⟨10.1155/2015/359153⟩. ⟨hal-01183884⟩