The live attenuated Mycobacterium bovis strain, Bacille Calmette Guérin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to a significant reduction of Mycobacterium tuberculosis burden after aerogenic infection. Our studies indicated that BCG induced protection against pulmonary tuberculosis was independent of T cells and present as early as 7 days after vaccination. This protection showed longevity, as it did not wane when conventional T cell and TNF-α deficient mice were infected 30 days post-vaccination. As BCG induced mycobacterial killing after 7 days, this study investigated the contributions of the innate immune system after BCG vaccination to better understand mechanisms required for mycobacterial killing. Subcutaneous BCG inoculation resulted in significant CD11b+F4/80+ monocyte subset recruitment into the lungs within 7 days. Further studies revealed that killing of mycobacteria was dependent on the viability of BCG, because irradiated BCG did not have the same effect. Although others have identified BCG as a facilitator of trained innate immunity, we found that BCG reduced the mycobacterial burden in the absence of mechanisms required for trained innate immunity, highlighting a role for macrophages and neutrophils for vaccine induced killing of M. tuberculosis.Keywords: BCG—Bacille Calmette-Guérin vaccine; innate; lung; macropahge; mycobacerium tuberculosis.

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