Humoral and lung immune responses to Mycobacterium tuberculosis infection in a primate model of protection

Recently we reported (Mehra et al., 2013), that lung granulomas from Mycobacterium bovis Bacille Calmette–Guérin (BCG)-vaccinated cynomolgus macaques exhibit upon challenge with M. tuberculosis a more balanced expression of α- and β-chemokines, relative to comparable samples from sham-vaccinated animals by comparative transcriptomics. Here, we studied the recruitment of immune cells to blood and lungs in M. tuberculosis-infected macaques as a function of prior BCG-vaccination. Vaccination initially enhanced the levels of both macrophages and lymphocytes in blood. In contrast, significantly more CD4+ lymphocytes were later recruited to the lungs of sham-vaccinated animals compared with earlier times/BCG vaccinated animals. BCG-vaccination had a short-lived impact on the anti-M. tuberculosis response. M. tuberculosis continued to replicate in the lung even in the wake of increased CD4+ T cell recruitment to primate lungs, indicating that immune subversive mechanisms are key to its survival in vivo.