Bacillus Calmette-Guérin (BCG) is still the only vaccine available against tuberculosis. This live attenuated vaccine form of Mycobacterium bovis, is one of the most widely administered vaccines and has been shown to provide nonspecific protection against unrelated. In a pulmonary context, it has also been described that intracutaneous BCG immunization reduces susceptibility to certain infections in mice, notably those induced by Influenza A Virus and Streptococcus pneumoniae (Sp), by modulating the innate immune system. In our project we evaluated the efficiency of a local intranasal BCG immunization against Sp and the incidence on the local immune response compared to an intracutaneous immunization.

Mice were intranasally or intracutaneously immunized, or not, with BCG (for 6 weeks to 6 months) before being infected with Sp. Bacterial load in the lung and spleen (CFUs), cytokine expression, and survival rates were assessed. In vitro, Max-Planck Institute (MPI) cells, cells closely resemble alveolar macrophages, were infected or not with BCG before being co-infected with Sp. MPI phagocytosis and bactericidal/killing activity were evaluated by CFUs and confocal microscopy.

Mice intranasally immunized with BCG displayed greater protection against Sp infection compared to intracutaneously immunized mice, by reduced bacterial load in the lung, lower dissemination of the bacteria and increased survival rate. These results can be, in part, explained by alterations of alveolar macrophages activity. Indeed, in vitro co-infection of MPI with BCG and Sp led to an increase in macrophage phagocytosis and bactericidal activity. Similar protection was observed with Mycobacterium tuberculosis, the causative pathogen of tuberculosis.

Collectively, these data demonstrate that intranasal immunization with BCG protects against Sp infection by modulating the innate immune response and, more precisely, enhancing alveolar macrophage activity. This intranasal administration of BCG could represent a promising therapeutic approach against pulmonary bacterial infections.