Cutting Edge: Bacillus Calmette–Guérin–Induced T Cells Shape Mycobacterium tuberculosis Infection before Reducing the Bacterial Burden

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Abstract:

<p>BCG immunization alters the cell types targeted for early M. tuberculosis infection.Vaccine-induced CD4 T cells are required for this transfer of infection.T cell activation within the lung first occurs distal to sites of infection.Growing evidence suggests the outcome of Mycobacterium tuberculosis infection is established rapidly after exposure, but how the current tuberculosis vaccine, bacillus Calmette–Guérin (BCG), impacts early immunity is poorly understood. In this study, we found that murine BCG immunization promotes a dramatic shift in infected cell types. Although alveolar macrophages are the major infected cell for the first 2 weeks in unimmunized animals, BCG promotes the accelerated recruitment and infection of lung-infiltrating phagocytes. Interestingly, this shift is dependent on CD4 T cells, yet does not require intrinsic recognition of Ag presented by infected alveolar macrophages. M. tuberculosis–specific T cells are first activated in lung regions devoid of infected cells, and these events precede vaccine-induced reduction of the bacterial burden, which occurs only after the colocalization of T cells and infected cells. Understanding how BCG alters early immune responses to M. tuberculosis provides new avenues to improve upon the immunity it confers.</p>