The role of IL-18 in dendritic cell interactions with M. bovis Bacille Calmette-Guérin (BCG)
Résumé
INTRODUCTION. The initiation and maintenance of specific responses to infective agents depend on dendritic cells (DC) playing the role of antigen presenting cells. IFN-γ has been demonstrated to be crucial to antimycobacterial immunity. The production of this cytokine by Th1 cells is effectively enhanced by IL-18, however, the role of IL-18 in human responsiveness to M. bovis BCG vaccine remains poorly understood. AIM. We asked a question whether human IL-18 released by the recombinant BCG strain (rBCGhIL-18) influences DC driven response to mycobacterial antigens in healthy humans who were vaccinated with BCG in childhood. MATERIALS AND METHODS. Immature DC were obtained from CD14+ monocytes, separated by magnetic sorting and stimulated for 6-days with IL-4 and GM-CSF. Dendritic cell response to live rBCGhIL-18 and BCG strains was estimated on the level of DC receptors (flow cytometry) and cytokines (ELISA) in 24-h cultures. RESULTS. Both mycobacterial strains caused a significant decrease in specific dendritic cell DC-SIGN receptor and an increase in CD86 co-receptor of the immune synapse. Neither rBCGhIL-18 nor BCG changed the expression of CD40 and HLA-DR on DC. Recombinant rBCGhIL-18 but not nonrecombinant BCG enhanced the DC expression of CD80 co-receptor and production of IP-10 chemokine, which promotes T cell migration to lymph nodes. Recombinant rBCGhIL-18 stimulated the production of T cell activating IL-23 and regulatory IL-10 by DC more intensively than nonrecombinant BCG. CONCLUSIONS. The obtained results suggest that IL-18 can positively modulate adaptive immune response to BCG bacilli by the intensification of antigen presentation and regulatory functions of dendritic cells.