Protection against aerosol Mycobacterium tuberculosis infection using Mycobacterium bovis Bacillus Calmette Guerin-infected dendritic cells

In the lung, dendritic cells (DC) are key antigen-presenting cells capable of triggering specific cellular responses to inhaled pathogens, and thus, t hey may be important in the initiation of an early response to mycobacteria l infections. The ability of DC to enhance antigen presentation to naive T cells within the lungs was characterized with respect to Mycobacterium bovi s Bacillus Calmette Guerin (BCG) vaccination against M. tuberculosis infect ion. In vitro derived DC were infected with BCG, which induced their matura tion, as shown by the increased expression of MHC class II antigens, CD80 a nd CD86 co-stimulatory molecules. The synthesis of mRNA for IL-1, IL-6, IL- 12, IL-10 and IL-1 receptor antagonist was also enhanced. When administered intratracheally in mice, infected DC induced a potent T cell response and the production of IFN-gamma to mycobacterial antigens in the mediastinal ly mph nodes, leading to a significant protection against aerosol M. tuberculo sis infection. Intriguingly, although the vaccination schedule for BCG-infe cted DC was much shorter than subcutaneous BCG vaccination (7 days as compa red to 100 days), both types of vaccination showed similar levels of protec tion. These data confirm that DC can be potent inducers of a cellular immun e response against mycobacteria and support the concept of combining DC str ategies with mycobacterial vaccines for protective immunity against tubercu losis.